My examination of the infant is dominated by careful observation and very little of the poking, prodding, scratching, head-dropping maneuvers described in many classical writings. Most of my time is spent watching the infant, with some gentle touches, to assess level of consciousness, eye position and movement, facial symmetry and movement, head position, asymmetry of limb positions, onset of spontaneous movement, and so forth. Surely, of course, evaluation of tone, and reflexes has a role, but most of my examination is performed check details by

watching the infant carefully. It has been somewhat embarrassing for me at times, to watch visitors or trainees watch me watch the infant, when I felt that they expected to see much more. Stand

there and look, don’t just do something. The most notable example driving home this lesson is our changing concept over the years of the most important brain lesion affecting the preterm infant. In the 1970s and early 1980s, CT and first-generation ultrasonography identified IVH in 40%-50% of see more very low birth weight infants. Indeed, CT and ultrasonography are excellent for detection of these hemorrhagic lesions and their major complication, posthemorrhagic hydrocephalus. The efforts of my group focused heavily on these areas at this time. However, later in the 1980s, with improvements in ultrasonographic instruments, the findings of periventricular echodensities and subsequent echolucencies made it clear that “cystic” white matter injury, or periventricular leukomalacia (PVL), was common and in fact correlated better with subsequent neurological deficits than did IVH. Into the 1990s, more careful assessment of ultrasound scans revealed that PVL without subsequent echolucencies, “noncystic” PVL, was more common than realized and indeed could very be the dominant pathology in very low birth weight infants. With the advent of magnetic resonance imaging (MRI) in the late 1990s to early 2000s, the predominance of “noncystic” PVL and the relative infrequency of serious IVH and cystic PVL became clear. However, from the turn of the century to the present, advanced MRI (volumetric and diffusion-based methods)

has provided evidence for neuronal/axonal disease in preterm infants with PVL. This work challenged the long-standing distinction that preterm infants exhibit principally white matter disease and term infants, gray matter disease. Most recently, advanced human neuropathologic studies have delineated multiple neuronal/axonal abnormalities in preterm infants with PVL, and the concept of the “encephalopathy of prematurity,” a disorder of both white and gray matter, has evolved. To fully understand the nature and spectrum of pathology in preterm infants, we must return to the largely neglected neuropathologic study of the human brain, but now using advanced immunocytochemical and related molecular methods. An important example underlying this lesson is the preterm infant with PVL.