Anemia of Prematurity - Portal Neonatal

Periventricular Leukomalacia
Last Updated: February 7, 2003
Synonyms and related keywords: PVL, ischemic brain injury
AUTHOR INFORMATION Section 1 of 10
Author: Terence Zach, MD, Department Vice-Chair, Program Director, Associate 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
Terence Zach, MD, is a member of the following medical societies: American Academy of Pediatrics,
American Medical Association, and Nebraska Medical Association
Editor(s): Scott MacGilvray, MD, Associate Professor, Department of Pediatrics, Pitt County
Memorial Hospital; Robert Konop, PharmD, Director, Clinical Account Management, Ancillary Care
Management; Arun Pramanik, MD, Professor, Department of Pediatrics, Division of Neonatology,
Louisiana State University Health Science Center; Carol L Wagner, MD, Associate Professor,
Department of Pediatrics, Division of Neonatology, Medical University of South Carolina; and Neil N
Finer, MD, Director, Division of Neonatology, Professor, Department of Pediatrics, University of
California at San Diego
INTRODUCTION Section 2 of 10
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 two major theories propounded in the pathophysiology of PVL are: (1)
Watershed injury to the periventricular area due to a vascular insult and/or (2) maternal
chorioamnionitis or vasculitis with the production of cytokines leading to inflammatory damage to the
periventricular area in the developing brain.
PVL is a bilateral white matter lesion of 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. 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.
In addition to possible ischemic injury, PVL may be the result of edema fluid and hemorrhage causing
compression of arterioles in the white matter. Premature infants have impaired cerebrovascular
autoregulation and are susceptible to intracranial hemorrhage (ICH) as well as PVL. Many premature
infants have both PVL and ICH detected on ultrasonography.
In a recent 1999 epidemiologic study, Leviton et al provided a detailed careful analysis of maternal
infection, placental inflammation, and vasculitis and their relationship to PVL. They observed that fetal
inflammatory response, as reflected by fetal vasculitis (polymorphonuclear leukocyte infiltration in the
chorionic plate or umbilical cord), and not intra-amniotic infection damages the fetal brain. Maternal
infection (as reflected by maternal antibiotic administration) is also associated with fetal brain
damage, although not as a result of fetal brain infection. Furthermore, various maternal cytokines
have also been implicated in the pathogenesis of PVL.