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Updated: Aug 14, 2026
Mouse Models of Periventricular Leukomalacia
Published on: May 18, 2010
White matter injury in the preterm infant: an important determination of abnormal neurodevelopment outcome
1Department of Pediatrics, The University of Texas Southwestern Medical School, Dallas 75235-9063, USA. jperlm@mednet.swmed.edu
Insights
Periventricular white matter injury, including cystic periventricular leukomalacia (PVL) and white matter hemorrhage (WMH), significantly impacts premature infants. Understanding their pathogenesis is key to developing targeted preventative strategies for better neurodevelopmental outcomes.
Area of Science:
- Neonatal Neurology
- Perinatal Medicine
- Developmental Neuroscience
Background:
- Periventricular white matter injury (PVL and WMH) is a major cause of mortality and neurodevelopmental deficits in premature infants.
- PVL affects 3-4% of infants with birth weight < 1500g, linked to vascular factors and oligodendrocyte vulnerability.
- WMH associated with PV-IVH occurs in 10-15% of infants with birth weight < 1000g, appearing as venous infarction with secondary hemorrhage.
Purpose of the Study:
- To elucidate the pathogenesis of periventricular white matter injury in premature infants.
- To identify key contributors to PVL and associated WMH.
- To inform the development of targeted preventative strategies for improved neurodevelopmental outcomes.
Main Methods:
- Review of existing literature on the pathogenesis and clinical associations of PVL and WMH.
- Analysis of factors contributing to ischemia and oligodendrocyte vulnerability in PVL.
- Evaluation of preventative measures for PV-IVH and associated white matter injury.
Main Results:
- PVL pathogenesis is multifactorial, involving vascular factors (hypotension) and oligodendrocyte susceptibility to neurotoxins.
- Clinical associations with PVL include chorioamnionitis, prolonged membrane rupture, asphyxia, sepsis, and hypocarbia.
- Antenatal glucocorticoids reduce severe IVH and white matter involvement; postnatal indomethacin shows promise in prevention.
Conclusions:
- Understanding the pathogenesis of PVL and WMH is crucial for developing effective preventative strategies.
- Neurodevelopmental outcomes are generally poor with extensive white matter injury, but more favorable with lesser involvement.
- Targeted interventions are needed to mitigate the long-term neurodevelopmental deficits associated with these injuries.
Abstract:
Periventricular white matter injury, specifically cystic periventricular leukomalacia (PVL) and ipsilateral hemorrhage into white matter associated with periventricular-intraventricular hemorrhage (PV-IVH), contribute significantly to neonatal mortality and long-term neurodevelopmental deficits in the premature infant. The first lesion PVL occurs in approximately 3-4% of infants of birth weight (BW) < 1500 grams. It manifests either as a focal or diffuse lesion within white matter. Although the pathogenesis of PVL is complex and likely multifactorial, principle contributors include vascular factors which markedly increase the risk for ischemia during periods of systemic hypotension and the intrinsic vulnerability of the oligodendrocyte to neurotoxic factors such as free radicals or cytokines. Clinical associations with PVL include a history of chorioamnionitis, prolonged rupture of membranes, asphyxia, sepsis, hypocarbia, etc. The vast majority of infants exhibit long-term neurodevelopmental deficits that affect motor, cognitive and visual function. The second lesion, the ipsilateral hemorrhage into white matter lesion associated with PV-IVH, occurs in approximately 10-15% of infants of BW < 1000 grams. The white matter injury appears to be a venous infarction with hemorrhage occurring as a secondary phenomenon. Prevention of this lesion has to include prevention of the associated PV-IVH. In this regard, the antenatal administration of glucocorticoids has been associated with a significant reduction in the sonographic incidence of severe IVH and the associated white matter involvement. The postnatal administration of indomethacin to high risk infants appears to hold the most promise at the current time in preventing this lesion. The neurodevelopmental outcome with extensive white matter injury is universally poor, affecting long-term motor and cognitive deficits; the long-term outcome is more favorable with lesser involvement. A clearer understanding of pathogenesis of both conditions is essential so as to provide targeted preventative strategies.
