Hemianopic Visual Field Defects in Children

Grade IV bleeds were once thought to be extensions of germinal matrix bleeds into the surrounding parenchyma,215 but are now thought to result from venous infarction. They are termed periventricular hemorrhagic infarction.601

To the surprise of many, IVH is generally more benign than PVL. However, while patients with mild hemorrhage and normal ventricular size (grades I to III have less than a 10% incidence of neurological sequelae),612 patients with enlarged ventricles associated with IVH have a 50% incidence of neurological sequelae215,553 that are related to the location and extent of the parenchymal injury.114,583 In one large study,583 only 26% of patients with grade III or IV hemorrhages survived.

Periventricular hemorrhage (PVH), a complication of IVH, is often conflated with PVL.74 Periventricular hemorrhage refers to the periventricular hemorrhagic necrosis caused by venous infarction.74,553,599 This lesion is distinguishable neuropathologically from PVL, an ischemic, usually nonhemorrhagic, and symmetrical lesion of the periventricular white matter. Unlike PVL, PVH results from early gestational injury and usually produces a unilateral lesion that is causally related to germinal matrix-IVH. The venous infarction associated with PVH is particularly prominent anteriorly, while PVL has a predilection for the arterial border zones, particularly the posterior region near the trigone of the lateral ventricles.

Despite their pathological differences, in vivo distinction is confounded by the fact that PVL can also be associated with secondary periventricular hemorrhage (termed hemorrhagic periventricular leukomalacia). Consequently, some studies have used hemorrhagic periventricular leukomalacia

(ischemic arterial periventricular leukomalacia with secondary hemorrhage) to designate periventricular hemorrhagic infarction (the anterior hemorrhagic necrosis caused by venous infarction). The end stage of PVL and PVH (also an ischemic condition) cannot always be reliably differentiated although the changes of PVL are usually symmetrical and bilateral, whereas the opposite is true for PVH.596

Hemianopic Visual Field Defects in Children

Children may display pure hemianopic defects, with normal fields on the contralateral side, or asymmetric (albeit bilateral) visual field involvement. Children with pure hemianopic defects usually have normal visual acuity, and if the defect is congenital, it may go unnoticed for many years. Congenital homonymous hemianopia is often discovered on a routine eye examination.572 Patients may have a history of being involved in accidents with automobiles approaching from the affected side, or of being tackled frequently by players approaching from the affected side when playing football, etc. Overall, patients with congenital hemianopia have minimal visual disability, whereas adults with acquired hemianopias are often severely disabled. This difference may hypothetically arise from the ability of the developing nervous system, but not the adult brain, to develop compensatory rewiring after prenatal damage, a phenomenon that has been well demonstrated in kittens.536,595 It may also arise from differences in the adaptive strategies that hemianopic patients develop to fixate targets within the blind areas of the

visual field (see below). Finally, an extrageniculostriate system could theoretically play a role.96

Trauma and tumors are the most common case of homonymous hemianopia in children.314 Most cases of ­congenital homonymous hemianopia are due to unilateral or asymmetric cerebral lesions, but congenital optic tract syndromes do rarely occur.381 Common structural causes are congenital lesions, such as porencephaly, arteriovenous malformations, and gangliogliomas. Cases of congenital hemianopia may be isolated or associated with other neurological abnormalities. Conversely, congenital hemiplegia is associated with a variety of visual problems.223,403 One study467 found that 75% of children with congenital hemiplegia had a homonymous hemianopia homolateral to the hemiplegic side. Associated lesions include a variety of hemispheric cortical lesions, including cerebral hemiatrophy, porencephaly of the posterior cerebral hemispheres, occipital lobe dysplasia,572 vascular malformations (e.g., Sturge–Weber syndrome, occipital arteriovenous malformations), colpocephaly, polymicrogyria, as well as prenatal injury to the periventricular white matter.

Congenital homonymous hemianopia should be suspected in patients with congenital hemiplegia.467 Sturge-Weber syndrome may cause homonymous hemianopia due to leptomeningeal malformations involving one occipital lobe, with or without facial port-wine stains259 (Fig. 1.22). Congenital homonymous hemianopia with occipital porencephaly is a recognizedcomplicationofneonatalisoimmunethrombocytopenia.111

Porencephalic cysts often show a distribution corresponding to a territory perfused by one of the major cerebral arteries, suggesting a vascular etiology (Figs. 1.6–1.8). They may also arise in areas of the brain into which intracerebral hemorrhages have dissected. Most of these abnormalities can be elucidated with CT, but occasionally, this modality may be falsely negative. Tychsen and Hoyt572 described two patients with congenital hemianopia in whom the results of CT were normal but MR imaging disclosed focal occipital dysplasia involving the striate cortex and underlying white matter.

Highly characteristic optic disc and nerve fiber layer changes termed homonymous hemioptic atrophy may be seen in some patients as a result of transsynaptic degeneration.258,259,269 These consist of band-shaped pallor or atrophy of the contralateral disc; the ipsilateral disc shows temporal pallor. Corresponding hemiretinal patterns of nerve fiber layer dropout are characteristically present. The contralateral eye shows intact arcuate nerve fibers above and below the disc but absent or sparse nerve fibers in the retinal sectors nasal and temporal to the disc. The ipsilateral eye shows sparse nerve fiber layers in retinal sectors above and below the disc. Current evidence supports the notion that the presence of these disc changes attests to the timing of the cortical lesion as being prenatal259,411 or perinatal rather than acquired later in life. The clinical elucidation of transsynaptic degeneration of the retinogeniculate pathway has been used to ascribe a prenatal onset to associated cerebral lesions. For example, Fletcher et al172 described a 24-year-old patient

Fig. 1.22  MRI scan of 12-year-old girl with Sturge–Weber syndrome and right homonymous hemianopia. (a) Note severe atrophic foci over parietal and occipital areas with overlying

venous malformation. (b) The left globe shows thickened choroid (arrow) corresponding to choroidal venous malformation seen on fundus examination

with recent onset of seizures who was found to have homonymous quadrantanopia with underlying occipital lobe ganglioglioma. Because the patient showed transsynaptic atrophy of retinal nerve fibers, the authors reasoned that these findings indicated that gangliogliomas may arise in utero and exist for many years before causing symptoms.

Patients with congenital homonymous hemianopia may show an afferent pupillary defect on the side contralateral to the cerebral lesion. These defects are rather small, measuring around 0.3 log units, with a neutral density filter. This afferent pupillary defect has been attributed to transsynaptic degeneration of the pupillomotor fibers. It appears that the pupillomotor fibers, which do not synapse at the lateral geniculate nucleus but at the pretectal area, may also be susceptible to transsynaptic degeneration.572 When an apparent defect is encountered in a patient with hemianopia, involvement of the contralateral lateral geniculate nucleus or optic tract should be considered.54,437

Generally, patients with congenital hemianopia appear to cope better with their deficit than those with lesions acquired in adult life. Patients with homonymous hemianopia may exhibit a variety of adaptive strategies to mitigate their visual handicap. Patients with either congenital or acquired lesions show diminished or absent head movements when fixating an eccentric target.622 The saccadic strategy for fixating eccentric targets appears somewhat different in patients with congenital lesions than in those with acquired lesions. Congenital hemianopes often produce a single large saccadic movement into the blind field that overshoots the intended visual target and then “finds” it as the eyes drift back. This may be a more effective adaptation than that is often seen in patients with acquired hemianopia, in which the patient makes multiple small saccades into the blind field until the target of interest is found.400 Acquired hemianopes, though, may also learn the single large saccade strategy.

Patients with congenital, but not acquired, hemianopia frequently manifest a head turn.260,267 We examined a 12-year- old boy with a left homonymous hemianopia who turns his chin far over his left shoulder when batting right-handed during baseball games. Some authorities have noted that when such a child is forced to assume a normal head position, certain visual tasks, especially those related to mobility, become more difficult, which suggests that such head turns have a compensatory adaptive function. Because the fixation point of the eyes does not change with this maneuver, this adaptation could serve to centralize the remaining visual field with respect to the body, or to position the head so that saccades could be used to capture a wider angle of hemianopic space.131,199,267,459 Alternatively, this unique form of torticollis may represent a nonpurposeful postural tonus imbalance of hemispheric origin whereby early loss of visual input from one field increases neck muscle tonus on one side.73 Mechanistically, a postural tonus would circumvent any

element of will or choice on the part of the individual; the head simply goes where the neck muscles pull it.

Many children with congenital hemianopia defects show an exotropic deviation.267 The exotropia may also be coincidental because neurologically damaged children are predisposed to strabismus.267 When the exotropic eye is on the side of the visual field defect, it serves a compensatory function by enabling the patient to have panoramic vision in the presence of harmonious anomalous retinal correspondence. Even when the exotropic eye is on the side of the intact visual field, a significant expansion of visual field results that may facilitate navigation. Thus, irrespective of whether the exotropia developed as a neurological defect or as an adaptation, we carefully check confrontation visual fields in children with constant exotropia and avoid strabismus surgery when a heminanopic defect is discovered.248

Patients with cortical visual loss from any cause may show asymmetric involvement of the cerebral hemispheres with corresponding asymmetry in their visual fields, with one hemianopic field allowing better visual function than the other. In infants and young children with lesions of the visual area of one cerebral hemisphere, a marked VEP asymmetry has been demonstrated for both flash and pattern testing.345 Patients suspected of hemianopic defects on the basis of cerebral lesions should be tested for the presence of smooth pursuit asymmetry, either with an optokinetic ROP (OKN) target, spinning of the patient, or eye movement recording. Saccadic tracking to the side of the lesion is a helpful diagnostic sign in patients with large lesions involving the parietal lobe.278

Increasingly, younger patients are prone to acquire cortical blindness or hemianopic defects as either a presenting feature or an associated symptom of AIDS. The causative lesion is most commonly progressive multifocal leukoencephalopathy, but opportunistic infections and neoplastic lesions are not unusual.

Evaluation of the visual fields in infants and small children is more difficult than in adults, especially when neurological disorders, mental retardation, or illness coexist. Some useful information about the visual fields can be gleaned utilizing a modification of confrontational methods referred to as evoked saccadic techniques. When we suspect that an infant or young child with hemiplegia or neuroimaging evidence of posterior hemispheric injury harbors homonymous hemianopia, we introduce a colored toy into the superior or inferior portion of the potentially hemianopic field and move it toward the vertical meridian. If a saccade toward the toy is consistently seen as the object reaches the midline, the diagnosis of homonymous hemianopia is confirmed. Kinetic perimetry has also been performed in infants.218,416,588 Newer diagnostic techniques such as saccadic vector optokinetic perimetry may provide a more accurate means to test visual fields in neurologically-impaired children.424a

Mayer et al389 utilized a modified perimetric technique with LED stimuli and a forced-choice observation procedure to quantitatively record the visual fields of normal infants ages 6–7 months. They also demonstrated the applicability of this technique to infants at risk of harboring field defects, such as those with hydrocephalus. However, such methods have not received widespread application and remain investigational at this point. As mentioned earlier, VEP measurements with hemispheric recordings can help delineate preferential or asymmetric hemispheric disorders associated with hemianopic field defects.345 Some children with neglect may have a pseudohemianopia (a bodyor gaze-dependent defect rather than a retinotopic defect). When looking leftward, these patients are unable to see objects in the left retinotopic field, but when looking rightward, they can see objects in the left field.327,429

Delayed Visual Maturation

DVM is diagnosed when a child fails to show the expected visual function for his age but does so spontaneously after a period of time. These infants may initially appear to have cortical blindness, with poor or no fixation, normal pupillary responses, and no nystagmus, but neuroimaging studies show no underlying cerebral insult. Some of these children have a history of prematurity, delayed motor development, or small size for gestational age. Because improvement of vision is mandatory to make the diagnosis, the condition can only be suspected initially, with confirmation of the diagnosis made retrospectively following visual improvement. It should be evident then that there is no such entity as DVM that does not show visual improvement. When an ophthalmologist “hedges” when giving a visual prognosis to the parents of an apparently blind infant, he at least partially, acknowledges the entity of DVM.227,234,274

A brief summary of some developmental aspects of vision is relevant as background information for this topic.69 The globe reaches adult size only after the first decade of life. The fovea is not mature at birth. The cone photoreceptors are immature, and the ganglion cells have not moved aside to form the foveal pit. The fovea reaches full maturity at 4 years of age.245 Myelination of the optic nerves begins at the lateral geniculate nucleus, reaching the orbital part of the optic nerve atterm,andcontinuesoverthefollowing2years.378 Myelination of the geniculostriate pathway begins in the 10th fetal month and is fully mature about 4 months postnatally.620 The rate of myelination appears to be hastened by light exposure.401 Thus, a preterm infant, on reaching chronological term, has more advanced myelination than a full-term newborn.268

Other molecular mechanisms of retinal and retinocollicular synapse maturation522,552 are physiologically active during this

period. The parvocellular layers of the lateral geniculate nucleus (color vision and high-grade acuity) reach adult maturity at 6 months of age; the magnocellular layers (low-contrast sensitivity and motion detection) reach maturity at 2 years of age.249 Postnatal growth and development of the brain is not associated with an increase in cell number, but rather reflects an increase in the size of individual cells, synaptic density, and interconnections. Synaptic density in the striate cortex increases over the first 8 months and then begins declining, reaching adult density at age 11 years.272 Cortical ocular dominance columns become adultlike at 6 months.20 Functional, behavioral, and neurophysiological aspects of visual function emerge to some extent in a parallel manner with the aforementioned anatomical and physiological developmental aspects. Pupillary reaction to light becomes apparent in 30-week-old premature infants.276 Accommodation and stereopsis begin to emerge at about 3 months of age.20 Ocular pursuit movements in neonates are saccadic, becoming smooth at 2 or 3 months of age.2 Rapid changes in the configuration of VEPs occur in the first few months of life, so that abnormal-looking responses may be normal for age. Most newborn infants demonstrate fixation and following of a near object, such as the examiner’s face. However, some neonates show significant delays in developing fixation and following. It is these visual “late bloomers” that typify the entity of DVM.

Lambert et al344 reported nine cases of “pure” DVM, excluding cases with ocular abnormalities, perinatal asphyxia, or structural cerebral abnormalities. With one exception, all infants showed normal VEPs to flash and pattern stimulation (despite being behaviorally blind), and all these showed normalization of vision at the end of the follow-up period, usually within a few months. Children with DVM exhibit normal acuity thresholds as measured by grating and vernier acuity.205 The authors concluded that intact pattern VEPs strongly indicate a good visual prognosis in such behaviorally blind infants. Skarf,528 in a discussion of the paper by Lambert and colleagues,344 advised that absence of a pattern or even a flash VEP in meeting the study’s criteria should not, however, necessarily be interpreted as a dismal prognostic sign. Lambert et al344 felt that the visual recovery could not be explained by foveal immaturity, delay in myelination, and synaptogenesis of the posterior visual pathway.344 Moreover, in view of the normal pattern visual evoked responses in all but the one patient who did not attain normal vision, delay in the maturation of the striate cortex was also considered an unlikely explanation of the poor vision. MR imaging of the optic nerve and chiasm in normal infants and those with delayed visual development showed no delay in myelination patterns, either in the neural visual pathways or elsewhere in the cortex. Lambert et al344 suggested immaturity of the higher visual association areas as the possible explanation. This suggestion may be supported by the observation that the phylogenetically older systems are myelinated first, with

myelination proceeding roughly in a rostral direction; the cortical association fibers are myelinated last.620

As a diagnostic label, DVM may be used in the narrow sense previously described or may be applied more broadly to include patients with various developmental abnormalities and ocular disorders. A trend for a broader application of the term emerged as experience has accumulated to justify this. Tresidder et al566 reported 26 cases of DVM but had a different inclusion criteria, including all cases of blindness without an ophthalmological cause. They subdivided the cases into three groups. Group 1 included infants with isolated DVM. This group was further subdivided on the basis of the presence or absence of perinatal problems. Group 2 included infants with neurodevelopmental abnormalities. Group 3 included infants with nystagmus. Visual recovery was fastest in group 1 infants without perinatal problems, of whom seven of eight recovered normal vision between the third and fourth month of life. None in group 2 attained normal vision, while patients in group 3 did so but later than group 1. All groups developed nystagmus concurrent with visual recovery; the nystagmus disappeared in group 1, with complete visual recovery, but persisted in group 3. The timing of visual recovery in this study (between the third and fourth month of life) has been noted to be synchronous with the emergence of geniculostriate-mediated visual functions, such as binocular vision, some orientation-specific responses, and smooth eye movements. Thus, while nystagmus is usually absent in DVM, both transient and persistent nystagmus are wellrecognized findings in some cases.59,207

As the foregoing studies indicate, DVM is most widely thought of as representing an isolated anomaly with total eventual recovery of vision. However, as early as 1947, Beauvieux48 pointed out that DVM may be further complicated by superimposed ocular or neurodevelopmental disorders that may render the eventual visual outcome variable. Fielder et al168,169 modified the classification of DVM provided by Uemura and colleagues573,574 and divided DVM into the following three types:

Type 1. Isolated DVM is diagnosed when the child is otherwise healthy, with no associated ocular or systemic disease. Visual recovery usually occurs within a year of age.

Type 2. This second type is diagnosed when the child has associated systemic disease, mental retardation, or other neurodevelopmental disorders. This type includes infants who may be small for gestational age or premature children321 with associated delays in their general motor development.94 Kivlin et al321 suggested that visual inattentiveness in a preterm infant is a harbinger of generalized neurological problems more so than in full-term infants. Also included are children with organic brain damage, such as anoxia, hypoglycemia, Aicardi syndrome, tuberous sclerosis. Infants in this group usually improve partially. Neonatal hyperbilirubinemia may depress the visual evoked responses within the

first year of life although the possibility of phototherapy as a confounding variable has not been definitively excluded.90 Infants exposed in utero to cocaine may similarly have DVM.204

Type 3. The third type is diagnosed when the child has associated ocular disease, such as bilateral cataracts, severe corneal opacities, colobomas, retinal dystrophy, optic nerve hypoplasia, or albinism. Affected children often have associated nystagmus. The visual impairment in such children may appear early on to be out of proportion to the ocular defect per se but improves proportionately with time. Not all patients with the aforementioned disorders show improved vision over time, and no clinical features help distinguish those who improve from those who do not.166 The visual improvement has been postulated to result from posterior visual pathway maturation.166 Infants with no visual responses can show dramatic normalization after correction of myopic refractive errors.615

In the same way, children with organic visual loss in one eye (organic amblyopia) often develop a superimposed functional amblyopia (visual loss on a cortical basis)335 many children with bilateral ocular causes for their vision loss (e.g., coloboma, optic nerve hypoplasia, albinism, myopia) may have a superimposed component of DVM, as attested to by the observation that the vision in many of these children improves surprisingly in the first year of life. Of 11 such patients, Fielder et al166 reported significant, albeit limited, visual improvement in eight. It is tempting in this context to speculate on the pathophysiologic basis of visual improvement reported in infants with unilateral ocular disease (e.g., optic nerve hypoplasia, congenital glaucoma) after patching therapy.335,336 Could the visual improvement be due, at least in part, to a maturational phenomenon of the posterior visual pathway? Stated differently, is the partial recovery of vision observed in some patients with significant ocular disorders limited to those with bilateral disease, or can it also occur in unilateral ocular disorders? It is impossible to answer this question without an appropriately designed clinical trial.

Most patients with DVM have an unremarkable optic disc appearance. However, it has been noted that some patients with DVM may show gray discoloration of the optic discs (gray pseudo-atrophy of Beauvieux).48 Such children are usually either immature or have ocular albinism, with the grayish tint variably attributed to “the effect of contrast” between a normally pigmented disc and an albinotic fundus, or deficient myelin of the optic nerve. The gray appearance of the optic nerves originally led Beauvieux (1926, 1947) to speculate that this problem resulted from delayed myelination of the optic nerves. This discoloration should be distinguished from the grayish discoloration of the disc that may occur due to pigment on or within the disc substance that may be noted with melanocytoma or in several chromosomal abnormalities. Although Beauvieux attributed DVM to a

delay in myelination, he presciently used the term temporary visual inattention to describe this condition.50

In one study, MR imaging has shown that the overall myelination process appears delayed in infants with developmental delay as compared with normal age-matched infants.125 However, the overwhelming evidence suggests that the function of the retina, optic nerve, visual cortex, and saccadic eye movement systems are normal in infants with DVM.344,609 This hypothesis is supported by the observation that visual function of premature infants with cortical lesions is similar to that of infants without such lesions.134 This implies that a subcortical, subcortical, possibly collicular, extrageniculostriate system is responsible for vision in the neonate, a postulate supported by the clinical observation that vision is indeed abnormal in infants with subcortical lesions.135 According to this concept, visual recovery in DVM represents the emergence of a functioning geniculostriate system that takes place around 2–4 months of age.117 The notion of delayed myelination was reinforced by the finding that vision in infancy is subcortically mediated and that DVM may represent malfunction of the extrageniculostriate system (colliculus-pulvinar-parietal system), which subserves responses in neonates relating to detection, location, and orientation.167

Dubowitz et al135 suggested that lesions involving the thalamus have a more profound effect on the visual function than lesions of the visual cortex in infancy. This interpretation has been taken to imply that the extrageniculostriate system was responsible for early visual function and the striate system might not predominate until several months of age. The finding of a measurable delay in the development of pupillary responses implicates transient dysfunction of both cortical and subcortical visual systems in some patients.92 However, this interpretation appears to be incorrect. More likely, any profound visual disability associated with lesions of the thalamus in infants is due to their effect on visual attention mechanisms.234

Follow-up studies of children with DVM reveal a definite tendency toward the developmental problems, including global developmental delay as well as speech delay, hearing delay, and autistic tendencies, either concurrently or following visual improvement.11,88,169,212,268,495 For this reason, DVM has come to be viewed as a mild form of CVI by which injury to higher visual association centers that subserve visual attention may produce the behavioral profile observed clinically. Some neuroanatomic abnormalities may elude detection on the standard neuroimaging techniques used in infants, which are relatively insensitive to cortical abnormalities. Even in the absence of neuroimaging lesions, these children are at significant risk for neurodevelopmental and educational problems in the future. However, the much better visual prognosis than in patients with demonstrable cortical insults justifies a separate classification from the typical CVI.

Hoyt263 retrospectively reviewed 98 patients with isolated DVM who were followed for at least 3 years. Although 93 had 20/20 visual acuity, he found that 22 had a learning disability, 11 had attention-deficit hyperactivity disorder, 9 had seizures, 5 had cerebral palsy, 5 had psychiatric disorders, and 4 had autism. In nine children, repeat MR imaging showed minor gyral anomalies. Some children with a seizure focus in the frontal or parietal cortex appear to be “blind” despite the fact that no pathology can be identified in the eyes, the visual cortex, or the optic radiations.263 Hoyt concluded that DVM is attributable to a top-down injury (rather than the bottom-up injury that delayed myelination would imply) to higher cortical centers involved in processing visual attention and that the observed recovery is attributable to neural plasticity in the neonatal period.234 So, the notion that these are children who simply have 4 or 5 months of bad vision in early infancy is an oversimplification.

Because of limited processing resources, multiple objects compete at the same time in the visual field for neural representation. The brain appears to handle this competition in two primary ways: a bottom-up, stimulus-driven process, and a top-down, feedback attentional network.263,479 The visual attention network can be divided into a posterior system that subserves visual spatial attention and an anterior system that selects the stimulus of attention by providing “executive functions.”121,310 Although competition among objects in the visual environment must be resolved within the visual cortex, the top-down signals arise from areas of the brain outside the visual cortex. While the complete details of these areas have yet to be defined, primate and human studies point to similar basic substrates.121,310 The anterior system involved in selection of stimuli (executive functions) depends on the frontal cortex (frontal eye field and supplemental eye field areas), globus pallidus, caudate, and putamen, although other areas, especially in the posterior thalamus, may also be involved in gating visual attention.310,484 The posterior system appears to involve the inferior parietal cortex (probably more predominantly on the right), superior colliculus, and pulvinar.185,479 The capacity of the visual system to process information about multiple objects at any given moment in time is limited.569 A selective deficit in visual attention would nicely explain the normal VEPs and the capacity for the development of good visual acuity that characterizes DVM.

Some children who present with DVM may later prove to have congenital ocular motor apraxia. Infants with ocular motor apraxia may appear blind before acquiring head and neck control, which is a prerequisite to manifest the characteristic head thrusts.486 This is so because infants normally employ the saccadic system (which is defective in congenital ocular motor apraxia) to follow objects of regard (saccadic pursuit). Checking the vestibulo-ocular reflex by spinning such children around would produce only a slow phase of nystagmus; the fast phase would be expected to be defective.