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  • Print publication year: 2009
  • Online publication date: January 2010

25 - Neonatal stroke

from Section 4 - Specific conditions associated with fetal and neonatal brain injury



Perinatal stroke is increasingly recognized as an important cause of neurological morbidity including cerebral palsy, epilepsy, and behavioral disorders, as well as impaired visual function and language development. The estimated incidence of perinatal stroke is approximately 1/4000.

Perinatal stroke can be classified by blood supply (venous vs. arterial), age at stroke (fetal vs. neonatal), age at diagnosis (neonatal symptomatic vs. presumed perinatal/neonatal asymptomatic), or type of stroke (ischemic vs. hemorrhagic). Investigators have used a variety of terms, including “perinatal stroke,” “arterial ischemic stroke,” and “perinatal arterial stroke” to describe the conditions. A recent workshop of the National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke focused on refining the terminology. Ischemic perinatal stroke (IPS), now the term of choice, is defined as “a group of heterogeneous conditions in which there is focal disruption of cerebral blood flow secondary to arterial or cerebral venous thrombosis or embolization, between 20 weeks of fetal life through the 28th postnatal day, confirmed by neuroimaging or neuropathologic studies.” The group further divided IPS into three categories based on the timing of diagnosis: (1) fetal ischemic stroke, diagnosed prior to birth using fetal imaging or following stillbirth on the basis of neuropathologic examination, (2) neonatal ischemic stroke, diagnosed after birth and ≤ 28th postnatal day (including preterm infants), and (3) presumed perinatal ischemic stroke (PPIS), diagnosed in children > 28 days of age in whom the ischemic event is presumed to have occurred between the 20th week of fetal life and the 28th postnatal day.

Mercuri, E, Barnett, A, Rutherford, M, et al. Neonatal cerebral infarction and neuromotor outcome at school age. Pediatrics 2004; 113: 95–100.
Mercuri, E, Anker, S, Guzzetta, A, et al. Neonatal cerebral infarction and visual function at school age. Arch Dis Child Fetal Neonatal Ed 2003; 88: F487–91.
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: 39–46.
deVeber, GA, MacGregor, D, Curtis, R, et al. Neurologic outcome in survivors of childhood arterial ischemic stroke and sinovenous thrombosis. J Child Neurol 2000; 15: 316–24.
McLinden, A, Baird, AD, Westmacott, R, et al. Early cognitive outcome after neonatal stroke. J Child Neurol 2007; 22: 1111–16.
Sran, SK, Baumann, RJ. Outcome of neonatal strokes. Am J Dis Child 1988; 142: 1086–8.
Sreenan, C, Bhargava, R, Robertson, CM. Cerebral infarction in the term newborn: clinical presentation and long-term outcome. J Pediatr 2000; 137: 351–5.
Lee, J, Croen, , Lindan, C, et al. Predictors of outcome in perinatal arterial stroke: a population-based study. Ann Neurol 2005; 58: 303–8.
Lynch, JK, Nelson, KB. Epidemiology of perinatal stroke. Curr Opin Pediatr 2001; 13: 499–505.
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: 609–16.
Schulzke, S, Weber, P, Luetschg, J, et al. Incidence and diagnosis of unilateral arterial cerebral infarction in newborn infants. J Perinat Med 2005; 33: 170–5.
Lee, J, Croen, , Backstrand, KH, et al. Maternal and infant characteristics associated with perinatal arterial stroke in the infant. JAMA 2005; 293: 723–9.
Laugesaar, R, Kolk, A, Tomberg, T, et al. Acutely and retrospectively diagnosed perinatal stroke: a population-based study. Stroke 2007; 38: 2234–40.
Wu, YW, March, WM, Croen, , et al. Perinatal stroke in children with motor impairment: a population-based study. Pediatrics 2004; 114: 612–19.
Ozduman, K, Pober, BR, Barnes, P, et al. Fetal stroke. Pediatr Neurol 2004; 30: 151–62.
Levy, SR, Abroms, IF, Marshall, PC, et al. Seizures and cerebral infarction in the full-term newborn. Ann Neurol 1985; 17: 366–70.
Clancy, R, Malin, S, Laraque, D, et al. Focal motor seizures heralding stroke in full-term neonates. Am J Dis Child 1985; 139: 601–6.
Ramaswamy, V, Miller, SP, Barkovich, AJ, et al. Perinatal stroke in term infants with neonatal encephalopathy. Neurology 2004; 62: 2088–91.
Guzzetta, A, Mercuri, E, Rapisardi, G, et al. General movements detect early signs of hemiplegia in term infants with neonatal cerebral infarction. Neuropediatrics 2003; 34: 61–6.
Fitzgerald, KC, Williams, LS, Garg, BP, et al. Cerebral sinovenous thrombosis in the neonate. Arch Neurol 2006; 63: 405–9.
Wu, YW, Miller, SP, Chin, K, et al. Multiple risk factors in neonatal sinovenous thrombosis. Neurology 2002; 59: 438–40.
Fitzgerald, KC, Golomb, MR. Neonatal arterial ischemic stroke and sinovenous thrombosis associated with meningitis. J Child Neurol 2007; 22: 818–22.
deVeber, G, Andrew, M, Adams, C, et al. Cerebral sinovenous thrombosis in children. N Engl J Med 2001; 345: 417–23.
Roland, EH, Flodmark, O, Hill, A. Thalamic hemorrhage with intraventricular hemorrhage in the full-term newborn. Pediatrics 1990; 85: 737–42.
Wu, YW, Hamrick, SE, Miller, SP, et al. Intraventricular hemorrhage in term neonates caused by sinovenous thrombosis. Ann Neurol 2003; 54: 123–6.
Benders, MJ, Groenendaal, F, Uiterwaal, CS, et al. Maternal and infant characteristics associated with perinatal arterial stroke in the preterm infant. Stroke 2007; 38: 1759–65.
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: 88–96.
Groenendaal, F, Benders, MJ, Vries, LS. Pre-Wallerian degeneration in the neonatal brain following perinatal cerebral hypoxia–ischemia demonstrated with MRI. Semin Perinatol 2006; 30: 146–50.
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.
Takanashi, J, Barkovich, AJ, Ferriero, DM, et al. Widening spectrum of congenital hemiplegia: periventricular venous infarction in term neonates. Neurology 2003; 61: 531–3.
Takanashi, J, Tada, H, Barkovich, AJ, et al. Magnetic resonance imaging confirms periventricular venous infarction in a term-born child with congenital hemiplegia. Dev Med Child Neurol 2005; 47: 706–8.
Armstrong-Wells, J, Johnston, CS, Wu, YW, et al. Prevalence and predictors of perinatal hemorrhagic stroke. Pediatrics (in press).
Gould, DB, Phalan, FC, Breedveld, GJ, et al. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science 2005; 308: 1167–71.
Breedveld, G, Coo, IF, Lequin, MH, et al. Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly. J Med Genet 2006; 43: 490–5.
Gould, DB, Phalan, FC, Mil, SE, et al. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med 2006; 354: 1489–96.
Arkel, YS, Ku, DH. Thrombophilia and pregnancy: review of the literature and some original data. Clin Appl Thromb Hemost 2001; 7: 259–68.
Silver, RK, MacGregor, SN, Pasternak, JF, et al. Fetal stroke associated with elevated maternal anticardiolipin antibodies. Obstet Gynecol 1992; 80: 497–9.
Akanli, LF, Trasi, SS, Thuraisamy, K, et al. Neonatal middle cerebral artery infarction: association with elevated maternal anticardiolipin antibodies. Am J Perinatol 1998; 15: 399–402.
Gunther, G, Junker, R, Strater, R, et al. Symptomatic ischemic stroke in full-term neonates: role of acquired and genetic prothrombotic risk factors. Stroke 2000; 31: 2437–41.
Ballem, P. Acquired thrombophilia in pregnancy. Semin Thromb Hemost 1998; 24: 41–7.
Rigo, J, Nagy, B, Fintor, L, et al. Maternal and neonatal outcome of preeclamptic pregnancies: the potential roles of factor V Leiden mutation and 5,10 methylenetetrahydrofolate reductase. Hypertens Pregnancy 2000; 19: 163–72.
Hague, WM, Dekker, GA. Risk factors for thrombosis in pregnancy. Best Pract Res Clin Haematol 2003; 16: 197–210.
Chasnoff, IJ, Bussey, ME, Savich, R, et al. Perinatal cerebral infarction and maternal cocaine use. J Pediatr 1986; 108: 456–9.
Heier, , Carpanzano, CR, Mast, J, et al. Maternal cocaine abuse: the spectrum of radiologic abnormalities in the neonatal CNS. AJNR Am J Neuroradiol 1991; 12: 951–6.
Kurnik, K, Kosch, A, Strater, R, et al. Recurrent thromboembolism in infants and children suffering from symptomatic neonatal arterial stroke: a prospective follow-up study. Stroke 2003; 34: 2887–92.
Brenner, B, Fishman, A, Goldsher, D, et al. Cerebral thrombosis in a newborn with a congenital deficiency of antithrombin III. Am J Hematol 1988; 27: 209–11.
Hogeveen, M, Blom, HJ, Amerongen, M, et al.Hyperhomocysteinemia as risk factor for ischemic and hemorrhagic stroke in newborn infants. J Pediatr 2002; 141: 429–31.
Garoufi, AJ, Prassouli, AA, Attilakos, AV, et al. Homozygous MTHFR C677T gene mutation and recurrent stroke in an infant. Pediatr Neurol 2006; 35: 49–51.
Curry, CJ, Bhullar, S, Holmes, J, et al. Risk factors for perinatal arterial stroke: a study of 60 mother–child pairs. Pediatr Neurol 2007; 37: 99–107.
Lynch, JK, Han, CJ, Nee, , et al. Prothrombotic factors in children with stroke or porencephaly. Pediatrics 2005; 116: 447–53.
Miller, SP, Wu, YW, Lee, J, et al. Candidate gene polymorphisms do not differ between newborns with stroke and normal controls. Stroke 2006; 37: 2678–83.
Ment, LR, Ehrenkranz, RA, Duncan, CC. Bacterial meningitis as an etiology of perinatal cerebral infarction. Pediatr Neurol 1986; 2: 276–9.
Amit, M, Camfield, PR. Neonatal polycythemia causing multiple cerebral infarcts. Arch Neurol 1980; 37: 109–10.
Konishi, Y, Kuriyama, M, Sudo, M, et al. Superior sagittal sinus thrombosis in neonates. Pediatr Neurol 1987; 3: 222–5.
Jarjour, IT, Ahdab-Barmada, M. Cerebrovascular lesions in infants and children dying after extracorporeal membrane oxygenation. Pediatr Neurol 1994; 10: 13–19.
Pellicer, A, Cabanas, F, Garcia-Alix, A, et al. Stroke in neonates with cardiac right-to-left shunt. Brain Dev 1992; 14: 381–5.
Hernanz-Schulman, M, Cohen, W, Genieser, NB. Sonography of cerebral infarction in infancy. AJR Am J Roentgenol 1988; 150: 897–902.
Messer, J, Haddad, J, Casanova, R. Transcranial Doppler evaluation of cerebral infarction in the neonate. Neuropediatrics 1991; 22: 147–51.
Golomb, MR, Dick, PT, MacGregor, DL, et al. Cranial ultrasonography has a low sensitivity for detecting arterial ischemic stroke in term neonates. J Child Neurol 2003; 18: 98–103.
Cowan, F, Mercuri, E, Groenendaal, F, et al. Does cranial ultrasound imaging identify arterial cerebral infarction in term neonates?Arch Dis Child Fetal Neonatal Ed 2005; 90: F252–6.
Mader, I, Schoning, M, Klose, U, et al. Neonatal cerebral infarction diagnosed by diffusion-weighted MRI: pseudonormalization occurs early. Stroke 2002; 33: 1142–5.
Kuker, W, Mohrle, S, Mader, I, et al. MRI for the management of neonatal cerebral infarctions: importance of timing. Childs Nerv Syst 2004; 20: 742–8.
Shroff, M, deVeber, G. Sinovenous thrombosis in children. Neuroimaging Clin N Am 2003; 13: 115–38.
Vries, LS, Grond, J, Haastert, IC, et al. Prediction of outcome in new-born infants with arterial ischaemic stroke using diffusion-weighted magnetic resonance imaging. Neuropediatrics 2005; 36: 12–20.
Kirton, A, Deveber, G, Pontigon, AM, et al. Presumed perinatal ischemic stroke: vascular classification predicts outcomes. Ann Neurol 2008; 63: 436–43.
Weiner, SP, Painter, MJ, Geva, D, et al. Neonatal seizures: electroclinical dissociation. Pediatr Neurol 1991; 7: 363–8.
Scher, MS, Wiznitzer, M, Bangert, BA.Cerebral infarctions in the fetus and neonate: maternal–placental–fetal considerations. Clin Perinatol 2002; 29: 693–724, vi–vii.
Chalmers, EA. Perinatal stroke: risk factors and management. Br J Haematol 2005; 130: 333–43.
Baird, TA, Parsons, MW, Phanh, T, et al. Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke 2003; 34: 2208–14.
Vannucci, RC, Mujsce, DJ. Effect of glucose on perinatal hypoxic–ischemic brain damage. Biol Neonate 1992; 62: 215–24.
Clancy, RR. Prolonged electroencephalogram monitoring for seizures and their treatment. Clin Perinatol 2006; 33: 649–65, vi.
Monagle, P, Chan, A, Massicotte, P, et al. Antithrombotic therapy in children: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 645S–687S.
Jones, MW, Morgan, E, Shelton, JE. Primary care of the child with cerebral palsy: a review of systems (part II). J Pediatr Health Care 2007; 21: 226–37.
Juenger, H, Linder-Lucht, M, Walther, M, et al. Cortical neuromodulation by constraint-induced movement therapy in congenital hemiparesis: an FMRI study. Neuropediatrics 2007; 38: 130–6.
Sutcliffe, TL, Gaetz, WC, Logan, WJ, et al. Cortical reorganization after modified constraint-induced movement therapy in pediatric hemiplegic cerebral palsy. J Child Neurol 2007; 22: 1281–7.
Hoare, BJ, Wasiak, J, Imms, C, et al. Constraint-induced movement therapy in the treatment of the upper limb in children with hemiplegic cerebral palsy. Cochrane Database Syst Rev 2007; (2): CD004149.
Trauner, DA, Chase, C, Walker, P, et al. Neurologic profiles of infants and children after perinatal stroke. Pediatr Neurol 1993; 9: 383–6.
Wulfeck, BB, Trauner, DA, Tallal, PA. Neurologic, cognitive, and linguistic features of infants after early stroke. Pediatr Neurol 1991; 7: 266–9.
Tillema, JM, Byars, AW, Jacola, LM, et al. Cortical reorganization of language functioning following perinatal left MCA stroke. Brain Lang 2008; 105: 99–111.
Jacola, LM, Schapiro, MB, Schmithorst, VJ, et al. Functional magnetic resonance imaging reveals atypical language organization in children following perinatal left middle cerebral artery stroke. Neuropediatrics 2006; 37: 46–52.
Golomb, MR, deVeber, GA, MacGregor, DL, et al. Independent walking after neonatal arterial ischemic stroke and sinovenous thrombosis. J Child Neurol 2003; 18: 530–6.
Kirton, A, Shroff, M, Visvanathan, T, et al. Quantified corticospinal tract diffusion restriction predicts neonatal stroke outcome. Stroke 2007; 38: 974–80.
Koelfen, W, Freund, M, Varnholt, V. Neonatal stroke involving the middle cerebral artery in term infants: clinical presentation, EEG and imaging studies, and outcome. Dev Med Child Neurol 1995; 37: 204–12.
Estan, J, Hope, P. Unilateral neonatal cerebral infarction in full term infants. Arch Dis Child Fetal Neonatal Ed 1997; 76: F88–93.
Golomb, MR, Garg, BP, Carvalho, KS, et al. Perinatal stroke and the risk of developing childhood epilepsy. J Pediatr 2007; 151: 409–13.e2.
Trauner, DA, Nass, R, Ballantyne, A. Behavioural profiles of children and adolescents after pre- or perinatal unilateral brain damage. Brain 2001; 124: 995–1002.
Hetherington, R, Tuff, L, Anderson, P, et al. Short-term intellectual outcome after arterial ischemic stroke and sinovenous thrombosis in childhood and infancy. J Child Neurol 2005; 20: 553–9.
Mercuri, E, Spano, M, Bruccini, G, et al. Visual outcome in children with congenital hemiplegia: correlation with MRI findings. Neuropediatrics 1996; 27: 184–8.
Guzzetta, A, Fazzi, B, Mercuri, E, et al. Visual function in children with hemiplegia in the first years of life. Dev Med Child Neurol 2001; 43: 321–9.
Wen, TC, Rogido, M, Gressens, P, et al. A reproducible experimental model of focal cerebral ischemia in the neonatal rat. Brain Res Brain Res Protoc 2004; 13: 76–83.
Derugin, N, Ferriero, DM, Vexler, ZS. Neonatal reversible focal cerebral ischemia: a new model. Neurosci Res 1998; 32: 349–53.
Renolleau, S, Aggoun-Zouaoui, D, Ben-Ari, Y, et al. A model of transient unilateral focal ischemia with reperfusion in the P7 neonatal rat: morphological changes indicative of apoptosis. Stroke 1998; 29: 1454–61.
Wen, TC, Rogido, M, Genetta, T, et al. Permanent focal cerebral ischemia activates erythropoietin receptor in the neonatal rat brain. Neurosci Lett 2004; 355: 165–8.
Wendland, M, Manabat, C, Fox, CK, et al. The blood–brain barrier is more preserved in neonatal versus adult rats following transient focal cerebral ischemia. J Cereb Blood Flow Metab 2003; 23: 169.
Manabat, C, Han, BH, Wendland, M, et al. Reperfusion differentially induces caspase-3 activation in ischemic core and penumbra after stroke in immature brain. Stroke 200; 34: 207–13.