Neonatal white matter injury

Stephen L Nelson Jr MD PhD (

Dr. Nelson of Tulane University School of Medicine received honorariums from Sunovian and LivaNova and consulting fees from Supernus and BioMarin.

Brittani Wild DNP APRN FNP-C (

NP Wild of Tulane University School of Medicine has no financial relationships to disclose.

Michael V Johnston MD, editor. (

Dr. Johnston of Johns Hopkins University School of Medicine has no relevant financial relationships to disclose.

Originally released April 6, 1994; last updated October 3, 2018; expires October 3, 2021

This article includes discussion of neonatal white matter injury, encephalopathy of prematurity, neonatal white matter injury, perinatal white matter injury, PVMI, periventricular leukomalacia, and PVL. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Neonatal white matter injury, formerly called periventricular leukomalacia, is the leading cause of cerebral palsy and other neurocognitive deficits in prematurely born children. Advances in neuroimaging and epidemiological studies have increased our insight into the pathophysiology of this condition. Although no cure currently exists, several clinical trials are ongoing with the aim to prevent disease or to improve long-term outcome. This article provides a comprehensive review of the clinical, pathological, and imaging aspects of neonatal white matter injury, and they discuss advances in research relevant to this condition. A case study involving a preterm infant is reviewed including maternal history, obstetrical history, and patient s NICU hospital course; the study demonstrates long-term outcomes that may be associated with neonatal white matter injury.

Key points


• Neonatal white matter injury is the leading cause of cerebral palsy in children with extreme prematurity.


• Developmental and cell-specific vulnerability play a key role in the pathogenesis of neonatal white matter injury.


• Magnetic resonance imaging is an important diagnostic and prognostic tool in the evaluation of children with prematurity and neurocognitive deficits.


• Prognosis and neurodevelopmental outcomes, such as cerebral palsy and intellectual ability, are related to the severity of neonatal white matter injury.

Historical note and terminology

The first description of neonatal white matter injury comes from Parrot, in which he described pale infarcts seen as yellowish or chalky plaques in the lateral corners of the periventricular white matter; softening of the plaques formed cavities, which did not communicate with the ventricles (Parrot 1868). Fifty years later, Schwartz re-described these lesions, but it was not until the early 1960s that Banker and Larroche named this lesion “periventricular leukomalacia” and described its clinical pathological correlations with immature and mature infants, hypoxia-ischemia, and spastic cerebral palsy (Banker and Larroche 1962). Later, Leviton and Gilles used the term “perinatal telencephalic leuco-encephalopathy” (Leviton and Gilles 1973). Banker and Larroche described neonatal white matter injury as periventricular cystic focal necrosis with loss of all cellular elements, surrounded by a diffuse, non-necrotic injury to the periventricular white matter. Volpe referred to this as “encephalopathy of prematurity” as there is increasing evidence for abnormal gray matter development in prematurely born infants with white matter injury (Volpe 2005). Some authors use the term “periventricular leukomalacia” only for cystic white matter lesions. Neuroimaging studies indicate a high prevalence of diffuse white matter lesions in prematurely born infants, and, therefore, the term “diffuse perinatal white matter injury” has also been used (Back 2001; Dyet et al 2006). In order to avoid confusion, we will use the terms “noncystic” and “cystic white matter injury” in this article.

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