Neuroimaging pp 531-583 | Cite as

Perinatal Brain Injury

  • Peter Winkler
  • Robert A. Zimmerman


Children with hypoxic-ischemic injury (HII) or hypoxic-ischemic encephalopathy (HIE) can have acute clinical problems, such as seizures, respiratory distress, or rapid deterioriation of consciousness. However, clinical presentation is commonly delayed. Neurological deficits might only become obvious months or years following the event.

Clinical assessment of the extent or severity of the acute event is of limited prognostic value in infants. The immature brain, although more vulnerable to certain adverse stimuli, has an astonishing potential for compensatory functional development.1 Neurological deficits become more obvious when motor, cognitive, and associative demands rise above the level of basic infant functions. Walking, talking, school performance, or refined tests can reveal the limits of the brain's compensatory capacity.2

HIE in infants can be approached by considering the three principal clinical settings: the preterm ventilated infant, the term infant following birth asphyxia, and the infant following intrauterine compromise. Factors that might initiate or predispose to HIE are intrauterine or perinatal infection, metabolic disease, edema, hemorrhage, hypotensive events, and emboli.

When HIE occurs in utero, it may appear as migration or gyration anomaly, cystic brain malformation, hypoplasia, or agenesis. Although a reliable estimate of the hypoxic-ischemic origin of a given lesion may be reached, it is important to be aware that reading the past from imaging presentations can be subject to uncertainty in individual cases.

Imaging modalities have recently become increasingly more sophisticated. Modern ultrasound with high resolution B-mode and color Doppler are effective tools capable of answering many questions about HIE that are posed in the neonatal period and early infancy. In the hands of an experienced and specialized examiner, ultrasound is particularly useful in ill-ventilated premature infants, while having little or no impact on the unstable state of these patients. In term infants, following severe asphyxia, computed tomography (CT) can be helpful when ultrasound is inconclusive. Beyond the immediate postnatal period, magnetic resonance imaging (MRI) is often the most informative and useful imaging modality. It is more versatile than any other method. Acute changes can be accompanied by abnormal brain lactate concentration, intracellular edema, vascular occlusion, or regional perfusion deficits, which can be displayed by more specialized MR techniques, such as MR angiography, MR spectroscopy, diffusion or perfusion imaging. In subacute or chronic HIE, it is helpful to increase the sensitivity for detecting hemorrhage by using a gradient-echo sequence (2D FLASH) for hemosiderin-related susceptibility effects.

Prediction of outcome can be expected to gain considerable impact with increasing sophistication of imaging. In the ill, preterm infant, consistently normal brain imaging constitutes by far the most reliable prognostic factor for normal neurological function beyond infancy.

Medical-legal issues increasingly center on the evidence of HIE supplied by imaging. There is the expectation that modern imaging will solve complex problems. Usually, interest concentrates on timing of hypoxic-ischemic events related to birth. Although many cases of hypoxia-ischemia can be assigned to in utero versus peri-or postnatal events, evaluation based on postnatal imaging should be of sufficient quality and subject to expert reading. In early in utero insults, some major problems encountered are infection versus infarction, malformation versus HIE, and the precise timing of an insult when there is a lack of adequate perinatal imaging.

Minor perinatal events—normally of little risk for inducing HIE—might be superimposed on an already damaged, infective, edematous, metabolically abnormal, or maldeveloped brain, and thus lead to a catastrophic or unfavorable outcome. Imaging appearances should therefore be supplemented by a history of prenatal risk factors and perinatal events. Appearances, such as hydranencephaly or periventricular leukomalacia, are usually linked to one period in the pre-, peri-, or postnatal time frame. Exceptions from this common denotation should be kept in mind and such patterns of brain damage should therefore be regarded as to whether they favor one particular period or clinical setting.


White Matter Preterm Infant Term Infant Hypoplastic Left Heart Syndrome Subcortical White Matter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Lewine JD, Astur RS, Davis LE, Knight JE, Maclin EL, Orrison WW. Cortical organization in adulthood is modified by neonatal infarct: a case study. Radiology 1994; 190: 93.PubMedGoogle Scholar
  2. 2.
    Levene M, Dowling S, Graham M, Fogelman K, Galton M, Phillips M. Impaired motor function (clumsiness) in 5 year old children: correlation with neonatal ultrasound scans. Arch Dis Child 1992; 67: 687.PubMedCrossRefGoogle Scholar
  3. 3.
    Johnston MV, Trescher WH, Taylor GA. Hypoxic and ischemic central nervous system disorders in infants and children. Adv Pediatr 1995; 42: 1.PubMedGoogle Scholar
  4. 4.
    Palmer C. Hypoxic-ischemic encephalopathy. Therapeutic approaches against microvascular injury, and role of neutrophils, PAF, and free radicals. Clin Perinatol 1995; 22: 481.PubMedGoogle Scholar
  5. 5.
    Cowan FM, Pennock JM, Hanrahan JD, Manji KP, Edwards AD. Early detection of cerebral infarction and hypoxic ischemic encephalopathy in neonates using diffusion-weighted magnetic resonance imaging. Neuro-pediatrics 1994; 25: 172.Google Scholar
  6. 6.
    Steinlin M, Dirr R, Martin E, et al. MRI following severe perinatal asphyxia: preliminary experience. Pediatr Neurol 1991; 7: 164.PubMedCrossRefGoogle Scholar
  7. 7.
    Baenziger O, Martin E, Steinlin M. Early pattern recognition in severe perinatal asphyxia: a prospective MRI study. Neuroradiology 1993; 35: 437.PubMedCrossRefGoogle Scholar
  8. 8.
    Barkovich AJ, Westmark K, Partridge C, Sola A, Ferriero DM. Perinatal asphyxia: MR findings in the first 10 days. AJNR 1995; 16: 427.PubMedGoogle Scholar
  9. 9.
    Keeney SE, Adcock EW, McArdle CB. Prospective observations of 100 high risk neonates by high field (1.5 Tesla) magnetic resonance imaging of the central nervous system. II. Lesions associated with hypoxic-ischemic encephalopathy. Pediatrics 1991; 87: 421.PubMedGoogle Scholar
  10. 10.
    Lorek A, Takei Y, Cady EB, et al. Delayed (“secondary”) cerebral energy failure after acute hypoxia-ischemia in the newborn piglet: continuous 48-hour studies by phosphorus magnetic resonance spectroscopy. Pediatr Res 1994; 36: 699.PubMedCrossRefGoogle Scholar
  11. 10a.
    Roth SC, Azzopardi D, Edwards AD, et al. Relation between cerebral oxidative metabolism following birth asphyxia and neurodevelopmental outcome and brain growth at one year. Dev Med Child Neurol 1992; 34: 285.PubMedCrossRefGoogle Scholar
  12. 11.
    Younkin D, Medoff-Cooper B, Guillet R, et al. In vivo 31P nuclear magnetic resonance measurement of chronic changes in cerebral metabolites following neonatal intraventricular hemorrhage. Pediatrics 1988; 82 (3): 331 - 336.PubMedGoogle Scholar
  13. 12.
    Berg RA, Aleck KA, Kaplan AM. Familial porencephaly. Arch Neurol 1983; 40: 567.PubMedCrossRefGoogle Scholar
  14. 13.
    Smit LME, Barth PG, Valk J, et al. Familial porencephalic white matter disease in two generations. Brain Dev 1984; 6: 54.PubMedCrossRefGoogle Scholar
  15. 14.
    Harding BN. Malformations of the nervous system. Greenfield’s neuropathology, 5th ed. New York, Oxford University Press, 1992.Google Scholar
  16. 15.
    Abe K, Matsuda I, Arashima S, Mitsuyama T, Oka Y, Ishikawa M. Ultrastructural studies in fetal I-cell disease. Pediatr Res 1976; 10: 669.PubMedCrossRefGoogle Scholar
  17. 16.
    Perlman JM, Burns DK, Twickler DM, Weinberg AG. Fetal hypokinesia syndrome in the monochorionic pair of a triplet pregnancy secondary to severe disruptive cerebral injury. Pediatrics 1995; 96: 521.PubMedGoogle Scholar
  18. 17.
    Larroche JC, Droulle P, Delezoide AL, Narcy F, Nessmann C. Brain damage in monozygous twins. Biol Neonate 1990; 57: 261.PubMedCrossRefGoogle Scholar
  19. 18.
    Chou YH, Tsou Yau KI, Wang PJ, Shen YZ, Lee CY. Multicystic encephalomalacia in a surviving monochorionic twin. Acta Paediatr Sin 1993; 34: 474.PubMedGoogle Scholar
  20. 19.
    Larroche JC, Girard N, Narcy F, Fallet C. Abnormal cortical plate (polymicrogyria), heterotopias and brain damage in monozygous twins. Biol Neonate 1994; 65: 343.PubMedCrossRefGoogle Scholar
  21. 20.
    Friede RL, Mikolasek J. Postencephalitic porencephaly, hydranencephaly or polymicrogyria. A review. Acta Neuropathol Bed 1978; 43: 161.CrossRefGoogle Scholar
  22. 21.
    Cruveilhier J. Anatomie pathologique du corps humain. Paris, Balliere, 1835.Google Scholar
  23. 22.
    Squier M, Keeling JW. The incidence of prenatal brain injury. Neuropathol Appl Neurobiol 1991; 17: 29.PubMedCrossRefGoogle Scholar
  24. 23.
    Sinha SK, D’Souza SW, Rivlin E, Chiswick ML. Ischaemic brain lesions diagnosed at birth in preterm infants: clinical events and developmental outcome [see comments]. Arch Dis Child 1990; 65: 1017.PubMedCrossRefGoogle Scholar
  25. 24.
    Trounce JQ, Shaw DE, Levene MI, Rutter N. Clinical risk factors and periventricular leukomalacia. Arch Dis Child 1988; 63: 17.PubMedCrossRefGoogle Scholar
  26. 25.
    Clancy RR. Neonatal seizures. In: Stevenson DK, Sunshine P, eds. Fetal and neonatal brain injury. Philadelphia, Decker, 1989.Google Scholar
  27. 26.
    Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976; 33: 696.PubMedCrossRefGoogle Scholar
  28. 27.
    Koivisto M, Blanca-Sequeiros M, Krause U. Neonatal symptomatic and asymptomatic hypoglycemia: a follow-up study of 151 children. Dev Med Child Neurol 1972; 14: 603 - 614.PubMedCrossRefGoogle Scholar
  29. 28.
    Nelson KB, Ellenberg JH. Apgar scores as predictors of chronic neurologic disability. Pediatrics 1981; 68: 36.PubMedGoogle Scholar
  30. 29.
    Koeda T. [Hypoxic brain damage and higher cortical dysfunction in children]. No To Hattatsu 1994; 26: 137.PubMedGoogle Scholar
  31. 30.
    Nelson KB, Swaiman KF, Russman BS. Cerebral palsy. In: Swaiman KF, ed. Pediatric neurology: principles and practice. St. Louis, Mosby, 1994.Google Scholar
  32. 31.
    Candy EJ. Hoon H, Capute AJ, Bryan RN. MRI in motor delay: important adjunct to classification of cerebral palsy. Pediatr Neurol 1993; 9: 421.PubMedCrossRefGoogle Scholar
  33. 32.
    Sugama S, Atsukawa K, Kusano K, et al. [Clinical consideration of patients with neonatal bilateral basal ganglia-thalamic lesion due to hypoxic ischemic encephalopathy]. No To Hattatsu 1994; 26: 295.PubMedGoogle Scholar
  34. 33.
    Rorke LB. Pathology of perinatal brain injury. New York, Raven Press, 1982.Google Scholar
  35. 34.
    Skullerud K, Westre B. Frequency and prognostic significance of germinal matrix hemorrhage, periventricular leukomalacia and pontosubicular necrosis in preterm infants. Acta Neuropathol Berl 1986; 70: 257.PubMedCrossRefGoogle Scholar
  36. 35.
    Banker BQ, Larroche J.-C. Periventricular leukomalacia of infancy: a form of neonatal anoxic encephalopathy. Arch Neurol 1962; 7: 386.PubMedCrossRefGoogle Scholar
  37. 36.
    Schouman Claeys E, Henry Feugeas MC, Roset F, et al. Periventricular leukomalacia: correlation between MR imaging and autopsy findings during the first 2 months of life. Radiology 1993; 189: 59.Google Scholar
  38. 37.
    Friede RL. Developmental neuropathology. Heidelberg, Springer; 1989.CrossRefGoogle Scholar
  39. 38.
    Pasternak JF. Hypoxic-ischemic brain damage in the term infant. Lessons from the laboratory. Pediatr Clin North Am 1993; 40: 1061.PubMedGoogle Scholar
  40. 38a.
    Schmorl G. Zur Kenntnis des Ikterus neonatorum, insbesondere der dabei auftretenden Gehirnveränderungen. Verh Dtsch Ges Pathol 1903; 6: 109.Google Scholar
  41. 39.
    van der Knaap MS, Barth PG. Discordant infantile encephalopathy with symmetrical thalamic calcifications in identical twins. Am J Med Genet 1994; 52: 218.PubMedCrossRefGoogle Scholar
  42. 40.
    Kupsky WJ, Drozd MA, Barlow CF. Selective injury of the globus pallidus in children with post-cardiac surgery choreic syndrome. Dev Med Child Neurol 1995; 37: 135.PubMedCrossRefGoogle Scholar
  43. 41.
    Ng HK. Hypotensive symmetrical hemorrhagic necrosis of the basal ganglia and brain stem. Pathology 1994; 26: 23.PubMedCrossRefGoogle Scholar
  44. 42.
    Dharker SR, Mittal RS, Bhargava N. Ischemic lesions in basal ganglia in children after minor head injury. Neurosurgery 1993; 33: 863.PubMedCrossRefGoogle Scholar
  45. 43.
    Eicke M, Briner J, Willi U, Uehlinger J, Boltshauser E. Symmetrical thalamic lesions in infants. Arch Dis Child 1992; 67: 15.PubMedCrossRefGoogle Scholar
  46. 44.
    Billard C, Dulac O, Bouloche J, et al. Encephalopathy with calcifications of the basal ganglia in children. A reappraisal of Fahr’s syndrome with respect to 14 new cases. Neuropediatrics 1989; 20: 12.PubMedCrossRefGoogle Scholar
  47. 45.
    Schuierer G, Kuriemann G, Bick U, Stephani U. Molybdenum-cofactor deficiency: CT and MR findings. Neuropediatrics 1995; 26: 51.PubMedCrossRefGoogle Scholar
  48. 46.
    Winkler P. Cerebrospinal fluid dynamics in infants evaluated with echographic color-coded flow imaging. Radiology 1994; 192: 431.PubMedGoogle Scholar
  49. 46a.
    Yokochi K, Aiba K, Kodama M, Fujimoto S. Magnetic resonance imaging in athetotic cerebral palsied children. Acta Paediatr Scand 1991; 80: 818.PubMedCrossRefGoogle Scholar
  50. 47.
    Paneth N, Rudelli R, Kazam E, Monte W. Brain damage in the preterm infant. Clin Developm Med 1994; 131.Google Scholar
  51. 48.
    Volpe JJ, Herscovitch P, Perlman JM, Raichle ME. Positron emission tomography in the newborn: extensive impairment of regional cerebral blood flow with intraventricular hemorrhage and hemorrhagic intracerebral involvement. Pediatrics 1983; 72: 589.PubMedGoogle Scholar
  52. 49.
    Volpe JJ. Intraventricular hemorrhage in the premature infant—current concepts. Part I. Ann Neurol 1989; 25: 3.PubMedCrossRefGoogle Scholar
  53. 50.
    Heschl R. Gehirndefect und Hydrocephalus. Vierteljahr-esschr Prakt Heilkd (Prag) 1859; 61: 59.Google Scholar
  54. 51.
    Obersteiner H. Ein porencephalisches Gehirn. Arb Neurol Inst, Wien Univ 1902; 8: 1.Google Scholar
  55. 52.
    Parrot J, Etude sur la stéatose interstitielle diffuse de l’encéphale chez le nouveau-né. Arch Physiol Norm Pathol 1873; 1: 530.Google Scholar
  56. 52.
    Yakovlev PI, Wadsworth RC. Schizencephalies: a study of the congenital clefts in the cerebral mantle. II. Clefts with hydrocephalus and lips separated. J Neuropath Exp Neurol 1946; 5: 169.PubMedCrossRefGoogle Scholar
  57. 53.
    Sims ME, Türkei SB, Halterman G, Paul RH. Brain injury and intrauterine death. Am J Obstet Gynecol 1985; 151: 721.PubMedGoogle Scholar
  58. 53.
    Yakovlev PI, Wadsworth RC. Schizencephalies: a study of the congenital clefts in the cerebral mantle. I. Clefts with fused lips. J Neuropath Exp Neurol 1946; 5: 116.PubMedCrossRefGoogle Scholar
  59. 54.
    Wigglesworth JS, Bridger JE. Neuropathological clues to the timing of early brain lesions. In: Lou HC, Greisen G, Falck J, eds. Brain lesions in the newborn. Copenhagen: Larsen Munksgaard, 1994.Google Scholar
  60. 55.
    Schwartz P. Birth injuries of the newborn. Arch Pediatr 1956; 73: 429.PubMedGoogle Scholar
  61. 56.
    Wigglesworth JS. Perinatal pathology: major problems in pathology. Philadelphia, W.B. Saunders, 1984.Google Scholar
  62. 57.
    Crome L. Multilocular cystic encephalopathy of infants. J Neurol Neurosurg Psych 1958; 21: 146.CrossRefGoogle Scholar
  63. 58.
    Volpe JJ, Pasternak JF. Parasagittal cerebral injury in neonatal hypoxic-ischemic encephalopathy: clinical and neuroradiologic features. J Pediatr 1977; 91: 472.PubMedCrossRefGoogle Scholar
  64. 59.
    Bresler. Klinische und pathologisch-anatomische Beiträge zur Mikrogyrie. Arch Psychiatr Nervenerkr 1899; 31: 566.Google Scholar
  65. 60.
    Anton G. Über die Beteiligung der basalen Gehirnganglien bei Bewegungsstörungen und insbesondere bei der Chorea mit Demonstration von Gehirnschnitten. Wien Klin Wochenschr 1893; 6: 859.Google Scholar
  66. 61.
    Orth J. Über das Vorkommen von Bilirubinkristallen bei neugeborenen Kindern. Arch Pathol Anat 1875; 63: 447.CrossRefGoogle Scholar
  67. 62.
    Rosales RK, Riggs HE. Symmetrical thalamic degeneration in infants. J Neuropath Exp Neurol 1962; 21: 372.PubMedCrossRefGoogle Scholar
  68. 63.
    Friede RL. Ponto-subicular lesions in perinatal anoxia. Arch Path 1972; 94: 343.PubMedGoogle Scholar
  69. 64.
    Gilles FH. Selective symmetrical neuronal necrosis of certain brain stem tegmental nuclei in temporary cardiac standstill. J Neuropath Exp Neurol 1963; 22: 318.CrossRefGoogle Scholar
  70. 65.
    Kast A. Zur Anatomie der cerebralen Kinderlähmung. Arch Psych Nervenerkr 1887; 18: 437.CrossRefGoogle Scholar
  71. 66.
    Cornblath M, Wybregt SH, Baens GS, Klein RI. Symptomatic neonatal hypoglycemia. Studies of carbohydrate metabolism of the newborn infant. Pediatrics 1964; 33: 388.PubMedGoogle Scholar
  72. 67.
    Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birthweight less than 1500 g. J Pediatr 1978; 92: 529.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Peter Winkler
  • Robert A. Zimmerman

There are no affiliations available

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