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Vol. 8 No. 10, October 2007
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NeoReviews Vol.8 No.10 2007 e418
© 2007 American Academy of Pediatrics

Cerebral White Matter Injury

The Changing Spectrum in Survivors of Preterm Birth

Stephen A. Back, MD, PhD*
Steven P. Miller, MDCM, MAS{dagger}

* Departments of Pediatrics and Neurology, Oregon Health & Science University, Portland, Oregon
{dagger} Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada

Despite advances in neonatal intensive care, periventricular white matter injury (PWMI) remains the most common cause of brain injury in preterm infants and the leading cause of chronic neurologic morbidity. Factors implicated in the pathogenesis of PWMI during prematurity include hypoxia, ischemia, and maternal-fetal infection. PWMI is recognized increasingly in term newborns who have congenital heart disease. The spectrum of chronic PWMI includes focal cystic necrotic lesions (periventricular leukomalacia [PVL]) and diffuse myelination disturbances. Information about the prevalence, severity, and distribution of white matter lesions has relied heavily on neuropathology studies of autopsy brains. However, advances in magnetic resonance imaging of the neonatal brain suggest that the incidence of PVL is declining; focal or diffuse noncystic injury is emerging as the predominant lesion. Insight into the cellular and molecular basis for these shifting patterns of injury has emerged from recent studies with several promising experimental models. These studies support the suggestion that PWMI can be initiated by impaired cerebral blood flow related to anatomic and physiologic immaturity of the vasculature. Ischemic cerebral white matter is susceptible to pronounced free radical-mediated injury that particularly targets immature stages of the oligodendrocyte lineage. The developmental predilection for PWMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible late oligodendrocyte progenitors. It is anticipated that new strategies for prevention of brain injury in preterm infants will develop as a result of improved recognition of changing patterns of injury that reflect specific types of cellular vulnerability.







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