Chapter 56 The brain and cerebral visual impairment
Numerous congenital and acquired disorders of the central nervous system affect children’s vision and many directly affect vital visual structures with varying disability. Others do not, but are associated with structural eye defects. In many parts of the world, especially in more developed countries, the prevalence of visual impairment in children due to brain disorders equals or exceeds that related to purely ocular disease. Many children with visual impairment due to brain disorders are multi-handicapped and their long-term potential for successful rehabilitation, education, employment, and independent-living is limited. Nevertheless, it is essential that their visual deficits and potential be carefully assessed in order that appropriate medical, rehabilitation, and educational services can be provided for them.
During the first month of embryogenesis, a neural plate is formed which invaginates into the neural groove and then fuses into a neural tube. Cephaloceles (defects in the skull and dura mater with extracranial extension of intracranial structures) are probably the result of a disturbance in the closure of the neural groove. Alternatively, they may occur as a postneuralation event with brain tissue herniating through the mesenchyme that will give rise to the cranium and dura. Three of the four major types of cephaloceles are of interest to ophthalmologists.
1. Occipital cephaloceles. In these portions of the occipital cortex and the occipital horn of the lateral ventricle herniate into the defect. Severe visual defects are associated both with the anomaly and the results of any surgical correction.
3. Nasal pharyngeal cephaloceles. These are uncommon, but visual function is almost always affected. The optic nerves and chiasm may be compromised as they are stretched when they extend into the sac of the defect. Optic nerve hypoplasia and retinal dysplasia and coloboma are frequent associations.
During the second month of gestation the forebrain (prosencephalon) is cleaved transversely into the telencephalon and diencephalon and sagittally into the cerebral hemispheres and lateral ventricles. Failure of differentiation and cleaving of the prosencephalon results in a group of disorders referred to as “the holoprosencephalies.” These are caused by both teratogens and genetic factors. Maternal diabetes is the most common recognized teratogen. Holoprosencephaly can be seen in a number of syndromes including Patau’s syndrome (trisomy 13), Edwards’ syndrome (trisomy 18), and de Morsier’s syndrome. Facial dysmorphism (hypotelorism and midline clefts) and numerous central nervous system anomalies are frequently associated (Fig. 56.1). Corpus callosum dysgenesis is common; unsurprisingly, therefore, so is optic nerve hypoplasia (see Chapter 51). Indeed, a significant subset of patients with septo-optic dysplasia may have a mild form of lobar holoprosencephaly.
Fig. 56.1 Complex brain anomaly in a 3-year-old girl born at 35 weeks gestational age. She has global developmental delays, intractable seizures, quadraparesis, severe visual impairment, nystagmus, and optic nerve hypoplasia. MRI reveals holoprosencephaly, absence of the corpus callosum, interhemispheric cyst, and anomalous ventricular system.
(Courtesy of Dr. Alejandra de Alba Campomanes.)
Between the second and fourth gestational months, the neurons in the ventricular and subventricular zones of the lateral ventricles proliferate and migrate to the cortical plates. This area of cell proliferation is known as the germinal matrix; here, stem cells give rise to the neurons and glial cells that will form the mature brain. Neurons in early embryogenesis migrate relatively short distances; neurons later in development migrate long distances across the intermediate zones. Neurons arriving first in the cortical mantle assume the deepest locations while later arriving neurons assume a more superficial location. Migration is facilitated by radial glial cells acting as guidelines. After arriving in the cortex neurons form discrete lamina and begin to establish synaptic connection with local and distant neurons. Aberrations in this normal migration and development process result in important neural abnormalities.1 In general, the resulting malformations can be divided into three categories − those due to:
Lissencephaly (smooth brain) occurs when neurons fail to migrate normally to the cortical mantle but remain in deeper layers. Over 90% of children with lissencephaly have seizures. Cobblestone lissencephaly occurs in at least three muscular dystrophy syndromes with important ocular features:
Fig. 56.2 A 10-year-old Vietnamese girl with severe developmental delays and hypotonia presents with bilateral cataracts, glaucoma, retinal detachments, and vitreous hemorrhages. (A). Axial MRI reveals dilated ventricles and pachygyria of the frontal cortex. (B) Sagittal MRI reveals pachygyria and polymicrogyria of frontal cortex, partial agenesis of the septum pellucidum, and hypoplasia of the brainstem. A diagnosis of Fukuyama’s disease was made.
(Courtesy of Dr. Alejandra de Alba Campomanes.)
Pachygyria is related to lissencephaly, but occurs at a later stage resulting in reduced numbers of gyri that are thick and underpopulated with neurons. Pachygyria of the occipital cortex may be associated with congenital hemianopia (see below). Pachygyria of the perirolandic and occipital areas is a prominent feature of Zellweger’s syndrome.
Polymicrogyria is the most common malformation of cortical development. It occurs as the result of the interruption of the late stages of neuron migration during the stages of cortical organization. The neurons reach the cortical mantle, but the deep layers are distributed which results in disorganized, multiple, and small gyri. Its effect on neurological function is less severe than the proliferation and migration anomalies. It may occur as an isolated focal anomaly of little consequence. The most common area is around the Sylvian fissure. However, it may also occur as a diffuse disorder affecting the entire brain. As an isolated and focal disorder it has been associated with congenital hemianopia (occipital cortex) and dyslexia (left frontal and temporal cortex). It is an important feature of several genetic syndromes including Aicardi’s syndrome, Joubert’s syndrome, Zellweger’s spectrum, Sturge-Weber syndrome, X-linked hydrocephalus, and 22q11.2 deletion syndrome. It is also associated with numerous metabolic disorders.2
Schizencephaly (agenetic porencephaly) is characterized by full thickness clefts spanning the wall of the cerebral hemispheres that are lined by gray matter and often surrounded by polymicrogyric cortex. The pathogenesis is incompletely understood although it is thought to represent an in utero injury to the germinal matrix during the second trimester before the hemispheres form. Previous reports that schizencephaly may be associated with mutations of the EMX2 homeobox gene, located on chromosome 10q26, and expressed in the germinal matrix has been challenged.3 The clefts may be unilateral or bilateral; the lips of the clefts may be open or closed. Seizures, hemiplegia, and mental retardation are the most common symptoms. Involvement of the occipital cortex is unusual but, when it occurs, especially when the cleft’s lips are fused, a homonymous hemianopia may occur. In contrast, patients with bilateral clefts are more likely to be severely retarded, severely limited by motor problems and blindness. The blindness is not usually cortical in origin, but due to optic nerve hypoplasia, a frequent accompanying anomaly in all forms of schizencephaly.
Children with congenital hemianopia show little evidence of visual dysfunction; the visual field defect is often discovered later in life on a routine eye examination. There may be a history of frequent bicycle or auto accidents, but many patients experience little effect on their daily lives. Therefore, the history may not be helpful in suspecting the presence of a congenital hemianopia. However, there are certain associated ophthalmologic and systemic findings that should alert the ophthalmologist to the possibility of a congenital hemifield defect.4
Most children with a congenital, but not acquired, hemianopia, turn their face toward the defective field when fixing on a target straight ahead of them (see Chapter 81). It is not clear how this compensates for the field defect, although the intact field is “centered” on the body by this maneuver. In any case, a persistent face turn in a child without incomitant strabismus or nystagmus with a null zone (the more common ocular causes of such a turn) should prompt an evaluation of the visual fields. In some cases, the face turn is accompanied by a constant, non-alternating exotropia;5 the exotropic eye is ipsilateral to the field defect (see Chapter 78). Theoretically, a large angle exotropia might significantly expand the binocular visual field with the appropriate sensory adaptation (harmonious anomalous retinal correspondence) although the evidence that it does so is incomplete. The frequent occurrence of exodeviations in neurologic disorders raises the question of the specificity of this finding. However, the unique combination of a face turn and exotropia ipsilateral to the face turn is highly suggestive of congenital hemianopia.
In addition to the visual field defect, face turn, and possible exodeviation, the most prominent ophthalmological finding in these children is localized changes in the optic disc and nerve fiber layer − “homonymous hemioptic atrophy” (hypoplasia). There is loss of retinal nerve fibers in the retinal sectors nasal and temporal to the disc in the eye contralateral to the field defect; in the ipsilateral eye the loss is superior and inferior. This subtle pattern of nerve fiber loss can be seen ophthalmoscopically or with OCT (optical coherence tomography).6 Examination of the optic discs will reveal a band-shaped atrophy of the contralateral disc and temporal atrophy of the ipsilateral disc. Since the lesions causing congenital hemianopia are almost always posterior to the lateral geniculate body, this points to transsynaptic degeneration of the retinogeniculate striate pathways. This has been thought to only occur with prenatal or perinatal insults, but recent experiments in non-human primates and OCT studies in patients with acquired hemianopias suggest that this is not the case.7
The more extensive the cortical anomaly, the more likely there will be other neurological disorders including hemiplegia, seizures, and developmental delays. The majority of patients with congenital hemiplegias will have an accompanying hemianopia. Syndromes in which congenital occipital cortex lesions with hemianopia occur include the Sturge-Weber syndrome, retinocephalic vascular malformation syndrome (Wyburn-Mason), and familial porencephaly.
Asymmetric injury to the periventricular ventricular white matter (periventricular leukomalacia, PVL) can present as an isolated congenital hemianopia, or, more commonly, with hemiparesis. The vast majority of cases of PVL present with bilateral involvement (see below). Rarely, congenital hemianopia associated with absence of the optic tract has been reported. It is unclear how this defect might occur.
Patients with congenital hemianopia are less visually disabled than those with acquired hemianopia. Our understanding of their adaptations and compensations accounting for their minimal disability is incomplete. The possibility that a face turn and/or exotropia could be compensatory has been cited above. A unique saccadic strategy limited to patients with congenital hemianopia allows them to search the blind field. This is distinctly more efficient than the multiple hypometric saccades made by the patient with an acquired hemianopia, but it can occur in congenital lesions (Video 56.1). Moreover, in children with acquired hemianopias the reaction time to initiate a saccade to explore the blind field is prolonged; this is not the case in congenital hemianopia.9