Articles
Periventricular Leukomalacia: An Important Cause of Visual and Ocular Motility Dysfunction in Children☆

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Abstract

The immature visual system in infants born preterm is vulnerable to adverse events during the perinatal period. Periventricular leukomalacia affecting the optic radiation has now become the principal cause of visual impairment and dysfunction in children born prematurely. Visual dysfunction is characterized by delayed visual maturation, subnormal visual acuity, crowding, visual field defects, and visual perceptual-cognitive problems. Magnetic resonance imaging is the method of choice for diagnosing this brain lesion, which is associated with optic disk abnormalities, strabismus, nystagmus, and deficient visually guided eye movements. Children with periventricular leukomalacia may present to the ophthalmologist within a clinical spectrum from severe cerebral visual impairment in combination with cerebral palsy and mental retardation to only early-onset esotropia, normal intellectual level, and no cerebral palsy. Optimal educational and habilitational strategies need to be developed to meet the needs of this group of visually impaired children.

Section snippets

Pathogenesis of Early Acquired White Matter Lesions

The pattern of cerebral injury found in newborn infants depends on the maturity of the brain at the time of insult. Damage to the immature brain at 24–34 weeks of gestation, either prenatally or (in prematurely born infants) perinatally, primarily affects the periventricular region. Ischemic and hemorrhagic lesions commonly occur in prematurely born infants. These lesions are frequently bilateral, with a fairly symmetrical distribution.

Cerebral Imaging Findings

Examination of the infant brain by ultrasound can be performed in the incubator, rendering this imaging modality the method of choice in the immature neonate. Although ultrasound detects intraventricular hemorrhage, germinal layer hemorrhage, hemorrhagic parenchymal infarction, and cystic changes, its sensitivity and specificity in detecting diffuse or subtle brain injury is poor.7, 52, 62, 66 When extensive cystic leukomalacia is identified, however, it is highly predictive of cerebral visual

Epidemiology

The reported incidence of periventricular leukomalacia as determined with ultrasound in the neonatal period varies from 16 to 26%.23, 73, 79 In 1997, Olsén et al published a population-based study from Finland, in which MRI verified the presence of periventricular leukomalacia in 32% of all children with a birth weight less than 1750 grams, but in none of the controls.64 Cerebral palsy was found in 9% of the study group. Visuospatial problems on neuropsychological testing was found in 60% of

Periventricular Leukomalacia and Cerebral Palsy

Cerebral palsy, or more specifically, spastic diplegia, is a well-known clinical sequel to periventricular leukomalacia, as this brain lesion interrupts the corticospinal tracts and the manifest functional deficit has caught the attention of pediatric neurologists (Fig. 1B).56, 80, 93 Between 72 and 90% of all children with spastic diplegia have periventricular leukomalacia.37, 51, 63

However, children with periventricular leukomalacia may escape cerebral palsy and exhibit only minor motor

Periventricular Leukomalacia and Mental Retardation

It has been demonstrated that preterm children without mental retardation and with normal MRI or with mild periventricular leukomalacia tend to have lower IQs than full-term controls.52, 65 Children with mental retardation (IQ < 70) in association with periventricular leukomalacia have bilateral extensive white matter reduction.52 Unilateral lesions can largely be compensated for with respect to cognitive function,86 and mild bilateral periventricular lesions are not associated with mental

Visual Dysfunction

In 1962, Banker and Larroche, who described the pathology of periventricular leukomalacia, suggested that the lesion could be expected to affect visual function, particularly the visual fields, as the axons in the optic radiation were interrupted.1 Several investigators in the 1970s found an association between infantile encephalopathy, cerebral palsy, strabismus, and cortical defects of sight.2, 14, 22, 69, 94 Visual evoked potentials have been employed to assess visual function in children

Refraction and accommodation

In children born preterm, myopia is a common refractive error,39, 47 and an association with ROP has been suggested.27 In children with periventricular leukomalacia, who have escaped severe ROP, hypermetropia, often in combination with astigmatism, seems to be common.43 The literature is sparse in describing refraction and accommodation correlated to lesions to the cerebral visual system. Hypermetropia has, however, been found in many studies on refraction in children with cerebral palsy.2, 71,

Identification of children with periventricular leukomalacia

Children with severe periventricular leukomalacia usually present with abnormal fixation, delayed visual maturation, and strabismus, frequently in combination with spastic diplegia and mental retardation. In these cases, the diagnosis has often already been confirmed by ultrasound in the neonatal period, or later with CT or MRI. These children, with severe functional deficits, are often already enrolled in neurological training programs.

However, the diagnosis may be a challenge in milder forms

Conclusion

Periventricular leukomalacia is a frequent cause of visual impairment in children born prematurely. Children with periventricular leukomalacia often have a concomitant spastic diplegia. These children may present to the pediatric ophthalmologist with early-onset strabismus. Their intellectual profiles are often uneven, and visuospatial problems are frequently observed. Delayed visual maturation, subnormal visual acuity, crowding, visual field defects, and cognitive visual dysfunction

Methods of Literature Search

MEDLINE/Pub Med and Ovid databases were searched, covering the years 1966 to 1999, and appropriate citations were reviewed. Search words comprised periventricular leukomalacia, risk factors, cortical visual impairment, cerebral visual impairment, cerebral palsy, strabismus, nystagmus, optic nerve hypoplasia. Additional references were obtained from the bibliographies of articles obtained from the MEDLINE search. Other sources included standard textbooks. The one non-English article was in

Outline

I. Pathogenesis of early acquired white matter lesions

A. Periventricular leukomalacia

B. Intraventricular hemorrhage, periventricular hemorrhagic infarction C. End stage white matter lesions

II. Cerebral imaging findings

III. Epidemiology

IV. Periventricular leukomalacia and cerebral palsy

V. Periventricular leukomalacia and mental retardation

VI. Visual dysfunction

A. Visual acuity

B. Visual fields

C. Color vision

D. Cognitive visual dysfunction

VII. Ocular findings

A. Refraction and accommodation

B. Optic

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      We hypothesized that children with CVI+CP would have more ophthalmic comorbidities and worse outcomes, particularly related to strabismus, compared to children with CVI−CP, because of a higher rate of periventricular leukomalacia (PVL) and hypoxic-ischemic encephalopathy (HIE) affecting the optic radiations. Although the neuroanatomic correlate(s) of childhood-onset strabismus are unknown, compromise of the optic radiations, which provide binocular input to the striate cortex, may be contributory.16-19 This is the only study to our knowledge that examines the ophthalmic effect of CP on CVI.

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      Subcortical visual impairment, such as PVL, is associated with worse clinical outcomes as compared with cortical visual impairment.7 PVL is proven to affect vision in children.6 Depending on the area and extent of affection of the lateral geniculate body and optic radiations, as well as the cause of affection, PVL is associated with variable ophthalmic manifestations.7

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