Cortical Visual Impairment

Abstract

After completing this article, readers should be able to: Vision loss caused by central nervous system damage often is referred to as CVI but also may be referred to as cerebral visual impairment or neurologic visual impairment. These terms refer to the fact that the primary defect may not necessarily be limited to the striate (primary visual) cortex and may affect other areas subserving vision, such as the visual associative cortex, optic radiations, and visual attention pathways. Although it is not yet certain which of these three terms best describes the visual deficit, it is clear that use of the label cortical blindness must be abandoned. That term not only evokes negative connotations for the child and the family but is inaccurate because in almost every instance, some degree of residual vision remains, and visual improvement can occur.CVI has become the greatest cause of pediatric visual impairment in developed countries (1)(2)(3)(4)(5) and is becoming increasingly prevalent in developing nations. CVI is a problem of increasing frequency for two primary reasons. First, the progress in neonatal care has resulted in improved survival of children who have brain damage from hypoxia. As a result, these children may suffer from CVI. (6)(7)(8) Second, the better outcomes associated with improved treatment of other causes of pediatric vision loss such as retinopathy of prematurity and congenital cataracts have diminished their roles as causes of pediatric blindness. (9)Various studies from the developed world illustrate the preeminent place of CVI among the causes of pediatric visual damage. Comparing current findings with previous prevalence studies, a population-based prospective study in five Nordic countries identified an increase from 11% to 23% in the relative frequency of CVI as a cause of pediatric blindness. (7) Along with optic atrophy, CVI accounted for 45% of cases of pediatric blindness in this study. In a recent survey of blind children in Ireland, the most common morphologic diagnoses were optic atrophy, optic nerve hypoplasia, and cortical blindness. (4) The Blind Babies Foundation of Northern California found that CVI was the leading cause of visual impairment in children younger than 5 years of age. (10)As recently emphasized by Hoyt, (5) understanding the mechanisms involved in pediatric CVI requires consideration that the pathologic processes may affect not only the primary visual cortex but also the associative areas, optic radiations, optic nerves, and even visual attention pathways.Hypoxic-ischemic brain injury is, by far, the most common cause of pediatric CVI. Matsuba and Jan (11) recently reported that hypoxia was the cause of CVI in 151 of 423 (35.7%) children diagnosed with CVI. Other authors have described similar figures in smaller series. (2)(12) The resulting pattern of injury is, to a large extent, defined by the age at which the insult occurs and differs in term and preterm children. (13)(14)(15) In term infants, the areas between circulation of the anterior and middle cerebral arteries and the medial and posterior cerebral arteries most typically are affected (watershed zones of the cerebral cortex). The loss of vascular flow autoregulation induced by hypoxia leads to hypoperfusion of the watershed territories, resulting in infarction of the frontal and parieto-occipital areas (parasagittal regions). The striate cortex is affected frequently but not exclusively. More anterior structures, such as the associative occipital visual areas and temporal and parietal cortices, commonly also are involved. (5)Unlike term infants, preterm babies rarely suffer parasagittal infarctions from hypoxia-ischemia. The periventricular deep white matter, where the germinal matrix is located, is involved when the insult occurs earlier, between 24 and 34 weeks of gestation. (16)(17) There is a transient, susceptible watershed zone in the periventricular white matter that later is replaced with the adult vascular configuration. (18) Capillaries in this region are prone to hemorrhage from hypoxia-ischemia. (16)(18) The characteristic injury is termed periventricular leukomalacia (PVL). The germinal matrix produces glial and neuronal cells that migrate eccentrically to populate the cerebrum. Immature oligodendrocytes and subplate neurons present around the ventricles at that moment are more vulnerable to ischemia than mature oligodendrocytes located elsewhere, which explains the specific location of the damage, believed to result from free radicals and decreased antioxidation. (19)(20)(21)(22)The optic radiations run precisely around the ventricles, and although this anatomic location partially explains the visual involvement, the pathogenesis appears to be much more complex. Circuits formed by these subplate neurons are necessary for the establishment and later maturation of visual connections between the thalamus and the cortex. (23)In the past, infections (Fig. 1) and hydrocephalus were the most common causes of CVI. (24) In more recent series, infections account for 11.8% to 15% of cases of CVI. (2)(5)(11)(12) The occipital cortex is more susceptible to damage produced by Haemophilus influenzae, the most common organism causing CVI. (25)(26)(27)(28)(29) Pneumococci and meningococci are other causative bacteria. (28)(30) Neonatal herpes simplex virus also causes ocular and cerebral visual problems. (31) The onset of visual impairment typically is late in the course of the infection, (1)(29) and multiple accompanying neurologic sequelae commonly occur. (32) The different mechanisms by which infection might injure the brain include thrombophlebitis, arterial occlusion, hypoxic-ischemic damage, venous sinus thrombosis, and hydrocephalus. (26)(27)(29)(33)Hydrocephalus, which has an incidence of about 1 in 1,000 during the first postnatal year, (34) can affect vision by causing optic atrophy through various mechanisms, but it also can also affect the posterior visual pathways that run close to the lateral ventricles. Furthermore, a combination of anterior and posterior visual involvement is frequent. A recent population-based study in Sweden revealed that due to an increase in the incidence of posthemorrhagic hydrocephalus in very preterm children, a previously decreasing incidence of hydrocephalus no longer is observed. Eighty percent of this population had ophthalmologic abnormalities such as strabismus, optic atrophy, and refractive errors, and 33% had visual impairment (visual acuity <0.3). (35) Houliston and associates (36) found that more than 50% of children who had CVI from hydrocephalus had higher cognitive visual deficits (“problems understanding and interpreting the visual world”). (17)Although ventricular dilatation can occlude the posterior cerebral arteries, (37) chronic distention of the posterior cortex is a more frequent mechanism by which hydrocephalus causes CVI. It is well known that shunt malfunction can cause CVI, but paradoxically, rapid correction by shunting also occasionally can produce CVI. (38)Head trauma is a significant cause of pediatric CVI (approximately 4% of cases in two studies). (2)(12) The damage may be transient or permanent. Shaken baby syndrome is a common cause of posttraumatic CVI. Fifty percent of the head injuries in a study published by Groenveld and colleagues (3) were the result of battering. Transient vision loss in children may occur after trivial injuries and typically is accompanied by headache, confusion, drowsiness, vomiting, and seizures. (39) A link with migraine has been mentioned by different authors, and this condition may be underdiagnosed because of the inability of young children to communicate their symptoms. (40) The pathophysiology is unknown, but an abnormal vascular response may result in vasospasm, ischemia, and edema. (39)(40)(41)Epilepsy and especially infantile spasms can cause central visual inattention (Fig. 2). Castano and associates (42) found some degree of visual improvement in only five of ten children who had severe visual inattention due to infantile spasms. Despite improvements at last follow-up, all of the patients retained significant visual impairment. Due to the severity of the visual and neurologic impairment, an objective measurement of visual acuity was possible in only one of the ten patients. Visual improvement was judged on the children's abilities to fixate and follow. The precise cause of visual impairment in patients who have infantile spasms is unknown, but it is likely the same mechanism that results in seizures and abnormal findings on electroencephalography. (39)(40)(41) Anticonvulsants are known to cause visual problems as well. (43)Congenital brain malformations (lissencephaly, schizencephaly, holoprosencephaly) also may be associated with CVI. (44) Metabolic and neurodegenerative disease, (32) hypoglycemia, (45) hemodialysis, (46) cerebrovascular accidents, and brain tumors (13) are among other reported causes of CVI.The diagnosis of CVI remains essentially a clinical one. (47) The possibility of CVI should be raised when there is greater delay in visual development than in other areas and when the degree of vision loss is unexplained by ocular findings. (48) Such a situation, paired with a characteristic clinical history such as hypoxia, should alert the clinician to the presence of CVI. In a typical case of CVI, results of the eye examination are normal, although this is not always the case. Concomitant ophthalmologic problems such as optic atrophy, nystagmus, and other conditions very frequently accompany CVI. This situation is exemplified by the preterm baby who is treated successfully for retinopathy of prematurity, but whose vision remains deficient and insufficiently explained by the ocular findings. In such a case, coexistence of some degree of CVI, often from PVL, should be considered.Habits that represent adaptations to the disease frequently are present in patients who have CVI. (1)(49)(50) Such habits are appropriately termed “neurobehavioral” signs and may aid in the diagnosis. To a large extent, many of these signs were identified and described by James Jan, a pediatric neurologist who has contributed enormously to the understanding of CVI in children. Light-gazing, a tendency to stare at bright light (eg, the sun or fluorescent lights), is frequent even in children who do not otherwise fixate. (51) Flicking the fingers in front of the eyes against the light for self-stimulation sometimes is seen. (52) Enigmatically, photophobia can be prominent and sometimes even coexist with light-gazing. (53) The explanation for this phenomenon is unknown, but thalamic or cortical damage may be responsible.A highly variable visual performance also is characteristic, with such variation even seen from hour to hour. (48) Children who have very limited vision may appear unexpectedly very responsive to color stimulation. (52) Such a response possibly is due to the bilateral cerebral representation of color, which is less likely to be eliminated unless the lesions are very extensive. Head shaking often is present, (54) as is pronounced head turns to search for objects, conceivably to make use of residual peripheral vision. (52) Visual function also appears to be better in more familiar environments. (48)Obtaining a measurement of visual acuity can be challenging in a child who suffers from accompanying neurologic deficits. If optotypes (standardized tables to test visual acuity) prove useless, preferential looking can be attempted (ie, Teller Acuity Cards, in which high-contrast gratings of different spatial frequencies are shown beside blank areas on the same card). The child usually prefers to fixate on the pattern of such cards, if seen. Even this method has limitations in testing patients who are unable to gaze directly because of eye or head movement problems, which are not uncommon in CVI. (55) It is possible to attempt to determine whether fixation or following capacity exists, but the inherent fluctuation of vision cannot be ignored in children whose vision can be influenced by fatigue, light conditions, or an unfamiliar environment. Therefore, obtaining an idea of a child's daily visual behavior is more important than assigning a numeric value to the visual acuity. Comments from the family as to how the child functions in his or her environment can be very useful.Most patients who have CVI have associated neurologic deficits. Khetpal and Donahue (12) found that 65.3% of children who had CVI had neurologic deficits. Whiting and associates (48) found that all of the patients in their study had some degree of neurologic deficit, and Wong (56) found deficits present in all congenital cases in her series. Epilepsy, cerebral palsy, hemiparesis, microcephaly, hydrocephalus, hearing problems, abnormal mental development, behavioral problems, myelomeningocele, progressive degenerative disorders, and hypotonia are among the reported anomalies, indicating that the damage may not be limited to the visual pathways. (2)(11)(12)(48)(56)Associated ocular findings, such as optic atrophy, nystagmus, strabismus, gaze palsy, and retinal disease, also are common. (2)(5)(11)(12)(48)(56) Although the absence of nystagmus in a case of congenital visual inattention suggests a cerebral cause, it is now known that the presence of nystagmus should not dissuade the clinician from diagnosing CVI in the appropriate setting. Nystagmus may result from concomitant anterior pathway disease, such as optic nerve or retinal disease, or it may indicate subcortical rather than cortical damage. (57) In fact, nystagmus is common in PVL. (58) When optic atrophy coexists with CVI, clinical judgment is needed to define the relative contribution of each factor to the visual limitation.Consideration of both the clinical presentation and neuroimaging findings often is sufficient to diagnose CVI. Nonetheless, certain entities should be included in the differential diagnosis for this disorder. The lack of interest characteristic of autism, the inability to generate saccades (fast eye movements) in a child who has oculomotor apraxia, or simply a delay in visual maturation may simulate CVI, but in these cases, the diagnosis of CVI is inappropriate.In many circumstances, neuroimaging can support or confirm the diagnosis of CVI, and imaging can aid in estimating the final visual outcome. The abnormalities seen on computed tomography (CT) scan and magnetic resonance imaging (MRI) for a child who has CVI are diverse and range from normal to substantially altered anatomy of the posterior visual pathways, depending on the cause, severity, and moment of the insult. Globalized cortical atrophy, ischemic encephalopathy, PVL, and structural malformations were the most common findings in a study by Khetpal and Donahue. (12) Diffuse cerebral atrophy was the most prevalent CT scan abnormality in a study by Lambert and associates. (59)Given the importance of neonatal hypoxia as a cause of CVI, imaging findings in this condition require discussion. First, the value of ultrasonography in evaluating preterm babies in the neonatal care unit deserves mention. This technique detects intraventricular and germinal layer hemorrhage, hemorrhagic parenchymal infarctions, and cystic changes. (16) The presence of cystic leukomalacia on ultrasonographic examination was found to be highly predictive of CVI. (60)(61)In older children who were born preterm, MRI is the most sensitive test for establishing damage to the periventricular white matter (Fig. 3). PVL is characterized by atrophic dilatation of the lateral ventricles and reduced volume of the periventricular white matter; the changes occur to a greater degree in the posterior aspect. (16)(62)(63) The severity of PVL has prognostic implications; a more severe PVL correlates with poorer future vision. (48)(64)(65) Lambert and associates (59) also found a positive correlation between the degree of involvement of the optic radiation on CT scan and MRI and a poor visual outcome. However, they found no correlation between visual recovery and changes in the striate and parastriate cortices. Casteels and associates (66) obtained similar results and described the myelination pattern as useful for predicting visual outcome.As stated, hypoxia in term infants tends to cause frontal and parieto-occipital infarctions. MRI later reveals cortical thinning and decreased underlying white matter, ex vacuo dilatation of the ventricles, ulegyria (misshapen, narrow gyri), and wedge-shaped infarctions. (67)The location of lesions in cases of profound hypoxia from cardiac arrest and hypotension may vary with gestational age. In preterm infants, the brainstem, cerebellum, and thalami are predominantly injured, often along with white matter damage. In babies born at term, the lateral thalami, posterior putamina (Fig. 4), hippocampus, and corticospinal tracts are affected, often along with damage to the lateral geniculate bodies and optic radiations. Due to limited survivability, these patterns are seen less frequently. (68)Despite the great value of MRI, in some cases, poor vision does not correlate with damage seen on imaging of the optic radiations or the primary and associative visual cortex. In these cases, it may be beneficial to use imaging to evaluate the damage to areas such as the frontal cortex, thalamus, inferior parietal cortex, superior colliculus, and pulvinar, which constitute the anatomic substrate for visual attention and may play a role in the pathogenesis of CVI. (69)Although it is not normally necessary, functional neuroimaging (Fig. 3) may complement MRI in studying CVI. Silverman and colleagues (70) found large areas of decreased cerebral blood flow using single-photon emission tomography in patients who had CVI in whom MRI had revealed no abnormalities.The role of VEP in confirming the diagnosis of CVI in children and predicting visual outcome has been addressed in many studies, and the subject is not free of controversy. Different technical methods, such as “flash” and “sweep,” are used to record potentials. Frank and Torres (71) did not find VEP valuable in diagnosing CVI because they were unable to identify differences in response between 30 children who had cortical loss of vision and 31 who had neurologic lesions and no visual involvement. Clarke and associates (72) found a low positive predictive value (45.1%) for flash VEP because 14 of 31 children who had abnormal responses remained impaired and low specificity (39.3%) because only 11 of 28 infants who showed improvement had had normal results on VEP. Other authors have demonstrated that a bad VEP result does not necessarily mean a poor future visual outcome. (73)(74)Nevertheless, other investigators have reported better utility of VEP in the evaluation of pediatric CVI. Taylor and McCulloch (75) reported that abnormal flash VEP results determined during the period of bad vision were useful in predicting a negative outcome. Kupersmith and Nelson (76) reported that the visually evoked response measured promptly after the insult is useful in predicting recovery. Good and Hou (77) found sweep VEP valuable in measuring visual acuity of children who had CVI using grate images as the visual stimulus.VEP appear to be a useful supplemental tool, but they have limitations, and clinicians should not to rush to predict a poor or good outcome solely on the basis of these findings. The procedure evaluates the integrity of the visual pathway but has limitations in accessing higher aspects of vision.Some improvement of vision virtually always occurs in children who have CVI. The mechanism by which improvement occurs continues to be a topic of interesting debate. In many cases, the likely explanation may be the presence of residual visual potential, which gradually improves over time. (78) Improvement also may result from the sparing of some areas rather than total destruction of visual cortical function at the time of injury. (48)Nonetheless, the fascinating changes observed in animals make it difficult to ignore the possibility that more sophisticated responses to early damage of central vision may occur in humans. Some studies strongly support this hypothesis. Research in cats whose visual cortex (areas 17, 18, 19) is ablated is particularly worthy of mention. The results could be summarized as anatomic and physiologic. After cortical lesions are produced, anterograde and retrograde tracing methods reveal a response that consists of increased anatomic projections from the retina through the thalamus to the posteromedial lateral suprasylvian extrastriate visual area in neonatal but not in adult cats. Also, the young cats, unlike the adult ones, demonstrate a functional compensation after cortical ablation. Single-cell neurophysiologic responses measured at least 6 months later in the posteromedial lateral suprasylvian cortex achieve normality. (79)(80) Although the cells in the latter area do not acquire the properties of the superior striate cortex, they do develop receptive field properties. (81) Similarly, young monkeys whose striate cortex is damaged, unlike older ones, demonstrate a capacity to respond to stimuli in the hemifield opposite the ablation as well as the ability to localize those stimuli with eye movements 2 to 5 years after the injury. (82)As mentioned, children afflicted with CVI seldom present with isolated lesions of the striate cortex. The associative areas of the occipital cortex or temporal or parietal cortices frequently are affected, sometimes predominantly. (69) Aside from abnormal visual acuity, many children who have CVI exhibit particular higher visual deficits (cognitive visual disorders), and these deficits can occur in conjunction with preserved visual acuity. (17)(83)(84)(85) Such deficits might result from lesions to the dorsal (parietal lobe, impaired ability to handle complex scenes) or the ventral (temporal lobe, impaired recognition) stream systems. (8) Saidkasimova and associates (86) published a series involving seven children who had impaired perception of movement, simultagnosia (one or some isolated elements of a visual scene can be recognized, but not the whole complex scene), visuomotor dysfunction, and impaired orientation. All exhibited some degree of periventricular white matter anomaly. It is important to recognize that CVI can involve much more than reduced visual acuity. (87)It has been suggested that evaluating the damage seen on neuroimaging to structures involved with mechanisms of visual attention may be of interest. A child who has poor vision potentially could have difficulties “choosing” among multiple presented images because of lesions involving visual spatial attention (frontal lobe, globus pallidus, caudate, putamen, and thalamus) or selection of stimulus for attention (inferior parietal cortex, superior colliculus, pulvinar) structures. This possibility has been discussed in detail by Hoyt, (69) and it may apply not only to cases of CVI in which the imaging findings of the striate and parastriate cortices and periventricular regions appear preserved, but also to more typical cases such as CVI from PVL. Recent evidence confirms that thalamic damage, for example, is frequent in PVL. (88)(89)Almost all children afflicted with CVI show some degree of visual improvement with time. Using different criteria, Matsuba and Jan (11) found overall improvement of visual acuity in 46% of patients, and Huo and associates (2) noted improvement in 60%. The level of vision achieved depends on many factors, including the cause, age of onset, and severity and type of injury. (1) Children who have subcortical damage seem to have a worse prognosis. In a retrospective study, Hoyt (5) found some recovery of vision in 78% of children who had striate cortex injury compared with 42% of children who had periventricular white matter involvement. Lambert and colleagues (59) found that imaging abnormality of the optic radiation correlated with a poor visual prognosis. Other causes of CVI such as bacterial meningitis and epilepsy have been associated in the past with a poorer outcome. (44)(56) However, factors other than cause (eg, timing of the insult, severity) must be considered for each case. For example, Huo and associates (2) did not find a correlation between cause and prognosis.More than 90% of children who have CVI remain visually handicapped despite some improvement of vision. Their neurodevelopmental outcomes other than vision also remain poor. (11)Early diagnosis and intervention are important in managing pediatric CVI. (3)(90) Groups who have substantial experience in caring for affected patients have made specific suggestions concerning rehabilitation. Reducing the amount of visual stimulation by presenting simple rather than crowded visual environments is believed to enhance vision in children who have CVI. Cueing by language, touch, and using contrasting colors are among the many useful strategies for optimizing residual vision. A multidisciplinary approach for each child is essential. (3)Because CVI almost is never an isolated problem, it is important to diagnose and treat any accompanying neurologic conditions. Pediatric neurologists, developmental pediatricians, and occupational therapists can be of help. Providing the best possible control of associated seizures that may interfere with visual function by optimizing their pharmacologic treatment also may alter visual behavior. Facilitating access to special services for concomitant cerebral palsy may help. (2)Sleep disorders affect children who have visual impairment, resulting not only from deregulation of the effect that vision is known to have on the sleep-wake cycle, but also from concomitant neurodevelopmental abnormalities. Detailed descriptions of the effects of melatonin and other treatment interventions are discussed elsewhere, (91)(92)(93)(94)(95) but we can testify to the benefits of enrollment in a pediatric sleep clinic.Only in limited circumstances is a treatment directed at the specific cause of CVI. Two examples are hydrocephalus or shunt blockage, in which the appropriate surgical intervention is therapeutic.The pediatric ophthalmologist or neuroophthalmologist is expected to play a role not only in assisting with the diagnosis of CVI but also in identifying associated ocular abnormalities and treating them when possible. For example, a child who has CVI and significant myopia may benefit from glasses. Every person involved in the care of an affected child must remember that the early promotion of visual development results in better outcomes. (90) Clinicians must direct the child as soon as possible to institutions capable of providing structured strategies and facilitate access to services provided by the health and educational systems.The author thanks Mrs. Monique Grimard and Dr Alexandre de Saint-Sardos for their invaluable aid in preparing this article.