Ординатура / Офтальмология / Английские материалы / Handbook of Pediatric Retinal Disease_Wright, Spiegel, Thompson_2006

invariably markedly delayed (of the order of 20–40 ms) when testing is done following the acute stage. Once acuity has recovered, P.VEP levels rise to moderate to good levels. The P.VEP tends to have a well-preserved waveform and is of moderate to good amplitude. During the acute stage when acuity is poor, the P.VEP is likely not to be detectable, or is very attenuated and delayed.80

In a follow-up study of 39 cases of childhood optic neuritis (average follow-up period, 8.8 years), it was found that only 20% had developed multiple sclerosis.115 In another study of 20 children who had had optic neuritis, with a mean age of onset of 9.4 years, it was found that 45% had significantly delayed VEPs at follow-up and that, on average, this was 9.3 years after the onset of the attack.81 In 64% of the eyes that showed significant delays, P.VEP latencies were increased by 15 to 35 ms, compared with 10 to 20 ms in optic nerve compression that is described next. This finding contrasts with optic neuritis in adulthood, where 90% of cases maintain significant delays in P.VEPs.78

OPTIC NERVE HYPOPLASIA (ONH)

Both flash and pattern VEPs are markedly attenuated, or not detectable, in cases of severe ONH. In moderate hypoplasia, the VEP (both to flash and large checks, 100 ) is variably attenuated, probably related to the degree of hypoplasia,117 and latency may be moderately increased.7 ONH can occur in albinism and is also frequently associated with de Morsier’s septooptic dysplasia, a syndrome linked with other midline brain abnormalities, particularly pituitary and hypothalamic dysfunction, and achiasmia. The flash VEP is valuable for indicating achiasmia in young children, a condition that may miss detection on routine CT or MRI scanning.212

OPTIC NERVE COMPRESSION

The P.VEP is usually degraded, attenuated, and mildly delayed (of the order of 10–20 ms) in optic atrophy caused by compressive, ischemic, or degenerative conditions. P.VEPs show a greater change compared with flash VEPs and often involve amplitude, latency, morphology, and occipital distribution.78 The authors have monitored a rare situation where the amplitude of P.VEPs (and PERGs) progressively reduced and became nondetectable concurrent with a gaze-evoked amaurosis when the patient (who had neurofibromatosis type 2) held his eyes in leftgaze. The tran-

sient blindness was caused by a mass at the apex of the left orbit compressing the optic nerve.196

Infantile osteopetrosis is an autosomal recessive disease caused by inadequate bone shaping by osteoclasts, which leads to excessive deposition of bone throughout the body. Patients are of short stature and characteristically have a pronounced forehead. The visual and auditory systems are adversely affected by the narrowing of the cranial foramina.67 The condition has a characteristic “bone-within-bone” radiologic appearance. The flash ERG has been reported to be attenuated;93,103 however, in a series by the authors, the majority of young children (13/15 patients) had normal mixed rod/cone flash ERGs.213 An abnormal flash ERG is likely to indicate associated neurological disease and would contraindicate a bone marrow transplant (BMT). However, it is worth noting that one of the cases had a pigmentary retinopathy and macular chorioretinal degeneration and did not show signs of central nervous system (CNS) degeneration 2 years after a BMT. The flash and P.VEP are abnormal in most cases of infantile osteopetrosis. In this same series, most patients had delayed (on average, 14 ms above laboratory norms) and attenuated flash VEPs. This finding can provide an early sign of anterior optic pathway compromise, often before detection by neuroimaging or fundoscopy.213

For craniofacial dysostosis, flash and P.VEPs can similarly provide an early indication of visual pathway dysfunction in syndromic and nonsyndromic craniosynostoses. Visual compromise is mainly ascribed to elevated intracranial pressure and physical distortion of the optic pathway. The authors have recently reviewed 130 craniofacial patients, most of whom have autosomal dominant syndromic conditions (e.g., Crouzon’s, Apert’s, Pffeifer’s, and Saethre chotzen syndromes). These syndromes have been associated with mutations in fibroblast growth factor receptor genes.173,232 In the authors’ series, Crouzon’s syndrome patients tended to have fewer ocular complications, compared with the other syndromes. Breathing difficulties, especially obstructive sleep apnea due to midfacial anomalies, may also contribute to the papilledema and optic neuropathy observed in these patients;172 this may explain why some cases show progressive deterioration in P.VEPs despite surgery to expand the vault. The authors have also observed recovery of small check P.VEPs after surgery and found that P.VEPs are a sensitive monitor of visual function in these instances. VEP changes can be conspicuous before optic pallor is frankly present and can

indicate functional changes when the appearance in chronically swollen discs is difficult to judge. Electrodiagnostic assessment has become an important part of the multidisciplinary protocol for assessing and managing such patients in the authors’ hospital.

Optic nerve glioma usually leads to a broadening, attenuation, and mild delay of the P.VEP from the affected eye. The transoccipital distribution of monocular P.VEPs can indicate any chiasmal involvement, caused by either backward spread of the disease process or primary involvement of the chiasm. Groswasser et al.73 found that the P.VEP P100 from the affected eye was, on average, delayed by about 20 ms and attenuated by 5 to 12 V, compared with the fellow unaffected eye. P.VEPs were much more sensitive than flash VEPs in showing eye differences and transoccipital asymmetries. In 20% of patients, occipital P.VEP asymmetry was mirror imaged when comparing eyes (called crossed asymmetry) and strongly indicative of compromised optic fibers subserving the temporal visual field of each eye. Interestingly, remission can occur occasionally in this condition, and visual function can improve spontaneously. Jabbari et al.96 stressed P.VEPs were useful in identifying patients with neurofibromatosis who also have optic nerve glioma. Primary involvement of the chiasm usually leads to marked attenuation and degradation of P.VEPs.

Hereditary Optic Atrophy and Cerebellar Ataxias

P.VEPs are commonly attenuated, degraded, and sometimes mildly delayed, in all forms of hereditary optic atrophy, although there may be differences between conditions in the tendency to which VEP components are affected.

LEBER’S OPTIC NEUROPATHY

In Leber’s optic neuropathy, there is bilateral subacute optic neuropathy linked with mutations in the mitochondrial genome in one of three nucleotide positions: 3460, 11778, or 14484. The illness is commonly similar to that in multiple sclerosis (MS) in females with 11778 mutation. P.VEPs are invariably markedly attenuated at the initial stage when visual acuity is poor, and although there may be some visual improvement subsequently, P.VEPs remain attenuated and degraded compared with controls.32,49,78

occurs and P.VEPs are moderately attenuated and marginally delayed.33 Vitamin E therapy for a Friedreich-like ataxia associated with RP has been shown to be effective in the short term.71 Reports of P.VEPs changes in olivopontocerebellar atrophy (OPCA) are somewhat variable. Some authors describe delayed and attenuated P.VEPs in about 20% to 50% of patients;159,204 however, others find P.VEPs to be normal.38

Drug Toxicity

VIGABATRIN

Vigabatrin is used to control infantile spasms and appears to achieve this antiepileptic effect by inhibiting action of gammaaminobutyric acid transaminase (GABA). However, it also produces a nonreversible loss of peripheral vision (in 1%–29% of adult patients) that is often binasal.52,231 Visual electrophysiology results are somewhat variable. There are reports of reduced EOG and oscillatory potentials,11,84 sometimes associated with cone system dysfunction109 and rod dysfunction.11 The current guidelines from the Vigabatrin Pediatric Working Party224 advise testing the cone system, and Harding et al.,85 endorsed by the American editorial board of Neurology, suggest that photopic cone-mediated flicker ERG is an effective screening protocol. Visual field testing is the most sensitive measure, but multifocal ERG and VEP testing also appear to be useful in detecting visual side effects of Vigabatrin.

OTHER ANTIEPILEPTIC MEDICATION

Other antiepileptic medicines have also been linked with visual field defects, including valproic acid, lamotrigine, gabapentine, diazepam, phenotoin, and carbamazepine.207,235 Carbamazepine and phenytoin reduce b-wave amplitude and OPs.15 Some of these drugs are often taken in combination, complicating the interpretation of studies on side effects.

INDOMETHACIN

This medicine is used as a prophylactic to reduce the incidence of severe intraventricular hemorrhage in very low birth weight infants (less than 1500 g) and as an antipyretic in newborns and infants. Prolonged use can cause changes in scotopic a- and b- waves.78

FIGURE 1-8. Schematic representation of crossed asymmetry, which characterizes chiasmal anomalies. The asymmetrical distribution over the occiput reverses if the other eye is stimulated. In achiasmia (left), the asymmetry is due to disproportionate activation of the ipsilateral hemisphere to the stimulated eye; in albinism (right), too many fibers cross at the chiasm and innervate the contralateral hemisphere.

treated for craniopharyngioma and, in 87% of the patients, there were preoperative ophthalmic signs such as optic atrophy, papilledema, or strabismus.111 In 44% of these patients, both flash and pattern VEPs were very attenuated and degraded or not detectable at all. In 20% of patients, there was a P.VEP crossed asymmetry, with poor temporal field responses from each eye. Also, 10% had an uncrossed asymmetry (same occipital distribution when stimulating each eye), indicating postchiasmal compression affecting one hemisphere only. In 2%, the VEPs from one eye only were markedly degraded and attenuated, indicating optic nerve compression, and P.VEPs were within normal limits in 24%. There was good agreement between the type of field loss indicated by P.VEPs and Goldmann visual field studies, except for a small minority of patients who had peripheral field loss confined to the upper quadrants. In these patients, the P.VEPs were deemed normal. Others have similarly emphasized the value of P.VEPs in detecting and monitoring chiasmal compression caused by craniopharyngioma or pituitary

tumors.27,59,78,90

the “albino” crossed asymmetry is best shown by using flash stimulation. In older children and adult albinos, the VEP abnormality is most conspicuous when using pattern-onset stimulation.5,44 Almost all albinos have nystagmus and foveal hypoplasia, and it is best to use large check sizes for eliciting P.VEPs. A small minority of albinos (8%–10%) may have nearnormal acuity and no nystagmus; however, they all show an albino-like crossed asymmetry for pattern-onset and pattern reversal stimulation.118 The authors have recently used half-field stimulation to estimate the proportion of fibers crossing at the chiasm using the VEP. It was found that this proportion can vary widely between patients and does not correlate well with the presence or absence of nystagmus or vision. Soong et al.202 compared five methods of gauging transoccipital asymmetry and commented on the interindividual variability in the methods; asymmetry was not detected by some techniques and was picked up by others. However, no patient with a confirmed molecular diagnosis of albinism gave symmetrical responses for all five paradigms. The variability, in part, can be related to optic nerve hypoplasia that can be marked in albinism. Optic nerve hypoplasia can be associated with very attenuated VEPs from which it is difficult to make judgment about distribution.

There is some debate whether iCSNB is allellic with Aland Island eye disease. Tremblay et al.217 have described an albinolike crossed asymmetry in iCSNB, using a bipolar interhemispheric electrode montage. The albino P-gene effects can also manifest as crossed asymmetry in Prader–Willi (PWS) and Angelman’s syndrome (AS).43,214 These syndromes are associated with the loss of imprinted gene expression from chromosome 15q11–q13; a loss from the paternal chromosome gives PWS and from the maternal chromosome, AS. The OCA2 gene can be involved in the common deletion site of these syndromes, and patients manifesting albinism are thought to have a deleterious mutation on their second P-gene allele as well.

Postchiasmal Dysfunction

GENERALIZED

In hypoxic, infective, ischemic, hydrocephalus, and most neurodegenerative conditions affecting the visual cortex, flash and P.VEPs are usually attenuated and degraded, although they tend to have normal, or near-normal, latencies. There are case reports