Encephalopathy of Prematurity Includes Neuronal Abnormalities

Abstract

The dominant encephalopathy of premature infants is considered generally to involve principally white matter.1 Periventricular leukomalacia (PVL) is the major form of white matter injury and consists classically of focal necrotic lesions, with subsequent cyst formation, and a less severe but more diffuse injury to cerebral white mater, with prominent astrogliosis and microgliosis but without overt necrosis. Injury to premyelinating oligodendrocytes appears to be a feature of the diffuse lesions,2 although the nature and extent of this cellular injury require additional study. This diffuse, noncystic white matter injury without focal necrosis is much more common than classic PVL. Results of neonatal imaging studies indicate that classic PVL with focal necrotic/cystic lesions occurs in ∼3% to 5% of very low birth weight premature infants (<1500 g), whereas the more diffuse noncystic lesions are demonstrable, on average, in 20% to 50%, depending on the imaging modality and the definition of abnormality (see ref 1 for review). Despite the longstanding emphasis on cerebral white matter among premature infants, numerous recent MRI studies of such infants at term and later ages suggest strongly that cerebral neuronal structures are abnormal frequently (see below). These observations are of particular importance because of the high incidence (∼50%) among survivors of prematurity of subsequent cognitive deficits without prominent motor deficits, a combination classically attributed in neurology to neuronal abnormalities rather than white matter abnormalities. The report by Lodygensky et al3 published elsewhere in this issue is focused on abnormal gray matter development, defined with volumetric MRI, among premature infants studied at 8 years of age and is highly relevant to the issue of neuronal abnormalities among premature infants. In addition, this work addresses the effect of postnatal hydrocortisone administration on subsequent structural and functional brain development. The focus on hydrocortisone is presented briefly next, and … Reprint requests to (J.J.V.) Department of Neurology, Fegan 1103, Children’s Hospital, 300 Longwood Ave, Boston, MA 02115. E-mail: joseph.volpe{at}childrens.harvard.edu