eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Periventricular Leukomalacia

Author: Terence Zach, MD, Department Vice-Chair, Professor, Department of Pediatrics, Section of Newborn Medicine, Creighton University
Coauthor(s): James C Brown, MD, Codirector of Pediatric Radiology, Assistant Professor, Department of Radiology, Creighton University School of Medicine
Contributor Information and Disclosures

Updated: Feb 14, 2008

Introduction

Background

Periventricular leukomalacia (PVL) is the most common ischemic brain injury in premature infants. The ischemia occurs in the border zone at the end of arterial vascular distributions. The ischemia of PVL occurs in the white matter adjacent to the lateral ventricles. The diagnostic hallmarks of PVL are periventricular echodensities or cysts detected by cranial ultrasonography. Diagnosing PVL is important because a significant percentage of surviving premature infants with PVL develop cerebral palsy (CP), intellectual impairment, or visual disturbances.

Pathophysiology

The pathophysiology of PVL is a complex process. PVL may occur because of ischemia-reperfusion injury to the periventricular area of the developing brain or because of cytokine-induced damage following maternal or fetal infection.

PVL is a white matter lesion in premature infants that may result from hypotension, ischemia, and coagulation necrosis at the border or watershed zones of deep penetrating arteries of the middle cerebral artery. Decreased blood flow affects the white matter at the superolateral borders of the lateral ventricles. The site of injury affects the descending corticospinal tracts, visual radiations, and acoustic radiations.
 
In addition to possible ischemic injury, PVL may be the result of edema fluid and hemorrhage that cause compression of arterioles in the white matter. Reperfusion injury by free radicals to developing oligodendrocytes in the fetal or premature infant's brain may play an important role in the pathogenesis of PVL.

Premature infants have impaired cerebrovascular blood flow autoregulation and are susceptible to intracranial hemorrhage (ICH) as well as PVL. Premature infants on mechanical ventilation may develop hypocarbia. Several studies have linked hypocarbia, particularly in the first few days of life, with the development of PVL.1,2

The relationship of maternal infection, placental inflammation, and vasculitis to the pathogenesis of PVL remains controversial. Some investigators have demonstrated an association of chorioamnionitis and cytokines with PVL although others have not.3

Following the initial insult, whether ischemia-mediated or cytokine-mediated, white matter damage occurs. The white matter damage likely occurs because of selective loss of oligodendrocytes.

Frequency

United States

  • Incidence of PVL ranges from 4-26% in premature infants in neonatal intensive care units (NICUs).
  • Incidence of PVL is much higher in reports from autopsy studies of premature infants.
  • As many as 75% of premature infants have evidence of PVL on postmortem examination.

Mortality/Morbidity

  • Cerebral palsy: Approximately 60-100% infants with PVL later develop signs of CP. Spastic diplegia is the most common form of CP following mild PVL. Severe PVL is frequently associated with quadriplegia.
  • Intellectual impairment: Varying degrees of intellectual impairment, developmental impairment, or both have been reported in association with PVL.
  • Visual dysfunction: Fixation difficulties, nystagmus, strabismus, and blindness have been associated with PVL. Some cases of visual dysfunction in association with PVL occur in the absence of retinopathy of prematurity, suggesting damage to optic radiations as causation.

Age

PVL occurs most commonly in premature infants younger than 32 weeks' gestation at birth.

Clinical

History

Periventricular leukomalacia (PVL) occurs most commonly in premature infants born at less than 32 weeks' gestation who have a birth weight of less than 1500 g. Many of these infants have a history of maternal chorioamnionitis. Most affected infants experience cardiorespiratory problems, such as respiratory distress syndrome or pneumonia, in association with hypotension or patent ductus arteriosus during their first days of life. Bacterial infection at birth also appears to be a risk factor.

Physical

Initially, most premature infants are asymptomatic. If symptoms occur, they usually are subtle. Symptoms may include the following:

  • Decreased tone in lower extremities
  • Increased tone in neck extensors
  • Apnea and bradycardia events
  • Irritability
  • Pseudobulbar palsy with poor feeding
  • Clinical seizures (may occur in 10-30% of infants)

Causes

  • Mechanically ventilated premature infants born at less than 32 weeks' gestation are at greatest risk for PVL.
  • Hypotension, hypoxemia, and acidosis may result in ischemic brain injury and PVL.
  • Marked hypocarbia in ventilated premature infants has been associated with increased risk of developing PVL.
  • Other associated risk factors include the following:
    • Placental vascular anastomoses, twin gestation, antepartum hemorrhage
    • Chorioamnionitis and funisitis
    • Sepsis
    • Maternal cocaine abuse

More on Periventricular Leukomalacia

Overview: Periventricular Leukomalacia
Differential Diagnoses & Workup: Periventricular Leukomalacia
Treatment & Medication: Periventricular Leukomalacia
Follow-up: Periventricular Leukomalacia
Multimedia: Periventricular Leukomalacia
References
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References

  1. Okumura A, Hayakawa F, Kato T, et al. Hypocarbia in preterm infants with periventricular leukomalacia: the relation between hypocarbia and mechanical ventilation. Pediatrics. Mar 2001;107(3):469-75. [Medline]. [Full Text].

  2. Wiswell TE, Graziani LJ, Kornhauser MS, et al. Effects of hypocarbia on the development of cystic periventricular leukomalacia in premature infants treated with high-frequency jet ventilation. Pediatrics. Nov 1996;98(5):918-24. [Medline].

  3. Kaukola T, Herva R, Perhomaa M, et al. Chorioamnionitis and cord serum proinflammatory cytokines: lack of association with brain damage and neurologic outcomes in very preterm infants. Pediatr Res. 2005;[Medline].

  4. Baud O, Foix-L'Helias L, Kaminski M, et al. Antenatal glucocorticoid treatment and cystic periventricular leukomalacia in very premature infants. N Engl J Med. Oct 14 1999;341(16):1190-6. [Medline].

  5. Canterino JC, Verma U, Visintainer PF, et al. Antenatal steroids and neonatal periventricular leukomalacia. Obstet Gynecol. Jan 2001;97(1):135-9. [Medline].

  6. Bass WT, Jones MA, White LE, et al. Ultrasonographic differential diagnosis and neurodevelopmental outcome of cerebral white matter lesions in premature infants. J Perinatol. Jul-Aug 1999;19(5):330-6. [Medline].

  7. Baud O, d'Allest AM, Lacaze-Masmonteil T, et al. The early diagnosis of periventricular leukomalacia in premature infants with positive rolandic sharp waves on serial electroencephalography. J Pediatr. May 1998;132(5):813-7. [Medline].

  8. Dammann O, Hagberg H, Leviton A. Is periventricular leukomalacia an axonopathy as well as an oligopathy?. Pediatr Res. Apr 2001;49(4):453-7. [Medline]. [Full Text].

  9. Dammann O, Leviton A. Brain damage in preterm newborns: might enhancement of developmentally regulated endogenous protection open a door for prevention?. Pediatrics. Sep 1999;104(3 Pt 1):541-50. [Medline]. [Full Text].

  10. de Vries LS, Regev R, Dubowitz LM, et al. Perinatal risk factors for the development of extensive cystic leukomalacia. Am J Dis Child. Jul 1988;142(7):732-5. [Medline].

  11. De Vries LS, Van Haastert IL, Rademaker KJ, et al. Ultrasound abnormalities preceding cerebral palsy in high-risk preterm infants. J Pediatr. Jun 2004;144(6):815-20. [Medline].

  12. Enzmann DR. Imaging of neonatal hypoxic-ischemic cerebral damage. In: Stevenson DK, Sunshine P, eds. Fetal and Neonatal Brain Injury: Mechanisms, Management, and the Risk of Practice. 2nd ed. Oxford, England: Oxford University Press; 1997:302-55.

  13. Hahn JS, Novotony EJ Jr. Hypoxic-ischemic encephalopathy. In: Stevenson DK, Sunshine P, eds. Fetal and Neonatal Brain Injury: Mechanisms, Management, and the Risk of Practice. 2nd ed. Oxford, England:. Oxford University Press;1997:277-286.

  14. Hayakawa F, Okumura A, Kato T, et al. Determination of timing of brain injury in preterm infants with periventricular leukomalacia with serial neonatal electroencephalography. Pediatrics. Nov 1999;104(5 Pt 1):1077-81. [Medline]. [Full Text].

  15. Haynes RL, Baud O, Li J, et al. Oxidative and nitrative injury in periventricular leukomalacia: a review. Brain Pathol. 2005;15:225-233. [Medline].

  16. Kuban K, Sanocka U, Leviton A, et al. White matter disorders of prematurity: association with intraventricular hemorrhage and ventriculomegaly. The Developmental Epidemiology Network. J Pediatr. May 1999;134(5):539-46. [Medline].

  17. Leviton A, Paneth N, Reuss ML, et al. Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants. Developmental Epidemiology Network Investigators. Pediatr Res. Nov 1999;46(5):566-75. [Medline].

  18. Liao SL, Lai SH, Chou YH, Kuo CY. Effect of hypocapnia in the first three days of life on the subsequent development of periventricular leukomalacia in premature infants. Acta Paediatr Taiwan. Mar-Apr 2001;42(2):90-3. [Medline].

  19. Murata Y, Itakura A, Matsuzawa K, et al. Possible antenatal and perinatal related factors in development of cystic periventricular leukomalacia. Brain Dev. 2005;27:17-21. [Medline].

  20. Paul DA, Pearlman SA, Finkelstein MS, Stefano JL. Cranial sonography in very-low-birth-weight infants: do all infants need to be screened?. Clin Pediatr (Phila). Sep 1999;38(9):503-9. [Medline].

  21. Shankaran S. Hemorrhagic lesions of the central nervous system. In: Stevenson DK, Sunshine P, eds. Fetal and Neonatal Brain Injury: Mechanisms, Management, and the Risk of Practice. 2nd ed. Oxford, England: Oxford University Press; 1997:151-64.

  22. Volpe JJ. Brain injury in the premature infant: overview of clinical aspects, neuropathology, and pathogenesis. Semin Pediatr Neurol. Sep 1998;5(3):135-51. [Medline].

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Further Reading

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Keywords

periventricular leukomalacia, PVL, ischemic brain injury, cerebral palsy, CP, hypotension, ischemia, coagulation necrosis, intracranial hemorrhage, ICH, hypocarbia, vasculitis, chorioamnionitis, cytokines, white matter damage, spastic diplegia, quadriplegia, nystagmus, strabismus, blindness, retinopathy of prematurity, maternal chorioamnionitis, respiratory distress syndrome, pneumonia, patent ductus arteriosus, placental vascular anastomoses, twin gestation, antepartum hemorrhage, sepsis

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Contributor Information and Disclosures

Author

Terence Zach, MD, Department Vice-Chair, Professor, Department of Pediatrics, Section of Newborn Medicine, Creighton University
Terence Zach, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

James C Brown, MD, Codirector of Pediatric Radiology, Assistant Professor, Department of Radiology, Creighton University School of Medicine
James C Brown, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Radiology, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Scott S MacGilvray, MD, Associate Professor, Department of Pediatrics, East Carolina University School of Medicine
Scott S MacGilvray, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Arun K Pramanik, MD, MBBS, Professor of Pediatrics, Director of Neonatal Fellowship, Louisiana State University Health Sciences Center
Arun K Pramanik, MD, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, National Perinatal Association, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina
Carol L Wagner, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American Medical Women's Association, American Public Health Association, American Society for Bone and Mineral Research, American Society for Clinical Nutrition, Massachusetts Medical Society, National Perinatal Association, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD, Head, Division of Neonatal-Perinatal Medicine, Professor, Departments of Pediatrics and Obstetrics/Gynecology, University of Connecticut School of Medicine
Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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