Children with PVL often display evidence of selective dorsal stream dysfunction, which selectively affects visuocognitive functions such as spatial awareness, attention, and visually-guided motion.21,139,140,141,397,398,509 Affected children may have difficulty distinguishing a line on the ground from a step, have difficulty combining tasks such as writing and listening, get frustrated if distracted while engaging in another activity, have difficulty choosing a toy in a toy box or against a cluttered background, get lost in the crowded visual scenes, and have difficulty walking down stairs or on uneven ground. These symptoms can sometimes be found even when MR imaging shows no evidence of periventricular leukomalacia or other abnormalities. Children with PVL and parietal/dorsal stream dysfunction often show visual field loss that is associated with an impaired ability to make accurate visually guided movements (or optic ataxia) especially of the lower limbs, accompanied by impaired simultaneous perception and, in some cases, with inaccurate saccades and, in others, impaired perception of movement. Cortical visual loss resulting from stroke can produce higher cognitive visual dysfunction, selectively affecting the dorsal or ventral stream.351

Selective dorsal stream dysfunction correlates with the finding that PVL shows a predilection for involving the lower visual fields.141,142,283 These findings could be explained by bilateral injury to the superior striate or extrastriate cortex. Galetta and Grossman found that horizontal meridian corresponds to the base of the calcarine fissures,186 which lie adjacent to the lesions of PVL. Horton and Hoyt256 observed that a lesion involving V2/V3 is uniquely able to produce a quadrantic visual field defect. If PVL involves higher cortical centers, associated injury to the primary visual cortex or dorsal stream injury involving higher cortical centers could obliterate the inferior visual fields bilaterally. Processing of biologic motion seems to be more severely affected.457 Although it is often written that the visual outcome of PVL is worse than that of CVI,210 many children in both groups have good visual acuity, and both groups show a large range of visual acuity. Because higher cortical dysfunction is what hobbles both groups, this distinction probably contributes little to the final visual prognosis.

Pathophysiology

In the premature brain, the periventricular region represents a transient watershed zone between the ventriculopetal and ventriculofugal branches of deep-penetrating arteries (so the optic radiations are more involved). In preterm infants, ischemic brain damage tends to predominantly affect the subcortical white matter adjacent to the lateral ventricles (the optic radiations) and the anterior horns of the lateral

ventricles (corticospinal tracts).35 Between the 27th and 34th week of gestation, a vascular watershed zone lies within the periventricular white matter, autoregulation is compromised in the immature vessels of the optic radiation. Until recently, periventricular leukomalacia was attributed to a watershed injury to periventricular white matter.35,76 This concept was based on the finding that ventriculofugal blood vessels in the brain (those coursing outward from the intraventricular and periventricular regions into the cerebrum) are poorly developed during the first two trimesters of gestation and that almost all blood supply comes from ventriculopetal arteries coursing inward from the surface of the brain.35,120,554,585 Recently, this watershed dogma has undergone progressive revision.330,435 Although vascular hypotension can produce ischemia within this subcortical arterial borderzone, recent evidence indicates that an increased metabolic activity, rather than vascular watershed distribution, may be primarily responsible for the selective ischemic injury to subcortical white matter.

Several pathogenetic factors have now been shown to contribute to white matter injury in the preterm newborn.618 First, the arterial vascular supply to the immature brain leads to arterial end zones within the deep periventricular white

matter.31,32,35,36,38,91,145,280,281,349,575 Second, the autoregulatory

mechanisms within the cerebral vasculature are immature. 32,599 Autoregulation is often absent in premature neonates and, because of the high incidence of lung immaturity, patent ductus arteriosus, and sepsis, mild cerebral hypoperfusion is common. This implies that fluctuations in arterial blood pressure induced during intensive care may be transmitted directly to the cerebral blood vessels, causing marked variations in cerebral blood flow. Consequently, specific regions within the deep white matter become highly vulnerable to ischemic and hemorrhagic injury. Third, it is now believed that the periventricular white matter, which is the site of oligodendrocyte proliferation in preparation for myelination, has high metabolic activity (highest perfusion, most mature metabolism, greatest glucose uptake) and therefore the greatest vulnerability to injury.35,599 Fourth, periventricular leukomalacia may result from ischemic injury to late oligodendrocyte progenitors, which show selective vulnerability to hypoxic ischemic injury in the third trimester.25,26 Preoligodendrocytes­ and oligodendrocyte progenitor cells seem to be more vulnerable to ischemic injury551 and ­infection304,305 than are mature oligodendrocytes.238 Under conditions of hypoxia-ischemia551 or infection,303–305,593,594 proinflammatory cytokines such as tumor necrosis factor-a, chemokines, reactive oxygen/nitrogen species, and trophic factors, induce apoptosis. Tumor necrosis factor-a cytotoxicity has been shown to play a major role in the pathogenesis of periventricular leukomalacia.364,454 The pattern of brain injury detected on MR studies of newborns who have suffered profound hypotension correspond closely to the patterns of