Review of cases presenting with microcephaly and bilateral congenital cataract in a paediatric cataract clinic.

PURPOSE: We reviewed all children presenting with microcephaly and bilateral congenital cataract in our paediatric cataract clinic, to identify their underlying diagnosis and clinical features that could help in early diagnosis of such conditions. METHODS: We screened our cataract database to collect data on all children presenting to our institute with cataract before 1 year of age for a period of 5 years (1997-2001) inclusive. We found 166 cases of cataract, of which 85 were bilateral. Of the 85 children with bilateral cataract, five also had microcephaly. The case notes of these five children were retrospectively reviewed for age at presentation, ocular and systemic examination findings, results of electro diagnostic testing, outcome of cataract surgery, and any additional investigation results. RESULTS: In our series, three children were diagnosed with early-onset Cockayne syndrome (CS2), one was diagnosed with Micro syndrome and one with Hallermann-Streiff syndrome. Electrodiagnostic testing was abnormal in four of the five cases, and growth failure was present in all five. There was a good outcome from surgery in the three children with CS2 and the child with Hallermann-Strieff. There was a poor outcome in the child with Micro syndrome. CONCLUSIONS: The presence of microcephaly in children presenting with bilateral cataracts in infancy is strongly suggestive of a syndromic cause. Early-onset Cockayne syndrome was the commonest underlying diagnosis in our series, but clinicians should be aware of other possibilities, and we discuss the differential diagnosis. Head circumference should be checked routinely in children with congenital cataract.

Vigabatrin-associated visual field defects in children.

PURPOSE: Vigabatrin (Sabril), a drug that blocks GABA transaminase, has been used in the treatment of epilepsy since 1989. There have been reports of irreversible constriction of the visual field in adult patients related to vigabatrin (VGB) therapy, resulting in reduced VGB usage in adults. Although used as a second or third line agent in adults, in children it is often considered as a first line treatment for several subgroups of seizures in spite of there being no way, in the majority of cases, to monitor visual fields. Some of these children have a pre-existing visual field defect as part of their primary disorder. We aimed to identify whether visual field loss due to VGB was occurring in our hospital. METHODS: We have studied the results of ophthalmic examination in 14 children on VGB at Great Ormond Street Hospital who were able to perform Goldmann visual fields. RESULTS: Ten of the 14 patients had constriction of their visual fields attributed to VGB. In addition there were 2 patients with suspicious visual field defects thought to be due to VGB. There was pre-existing visual pathway damage in 4 cases and in 2 of these optic disc pallor increased in association with constricted visual fields. However, the optic discs were normal in 7 patients in spite of visual field constriction. Visual acuity was generally normal in spite of gross visual field constriction. CONCLUSIONS: We believe that VGB should be used with great caution where there is pre-existing visual pathway damage. In other cases the benefits should be considered in relation to the risks, which include irreversible visual field damage. At present visual fields can only be monitored by perimetry, which is often not possible in children with epilepsy.

Saccadic strategies in children with hemianopia.

Multiple hypometric (undershooting) saccades are generally reported as a compensatory strategy in adults with homonymous hemianopia. However, hypermetric (overshooting) saccades have been reported to develop spontaneously as a beneficial strategy in response to predictable targets. We examined the saccades of 10 children (aged 5 to 16 years) with homonymous hemianopia to determine the type of compensatory eye-movement strategies employed 6 months to 16 years after hemianopia onset. Homonymous hemianopia was identified using perimetry and/or pattern visual evoked potentials and supported with results of neuroimaging. Eye movements were recorded using bitemporal electrooculography. Saccades were elicited to a red light source in a semipredictable paradigm. We found that hypermetria was not a consistent compensatory strategy in our patients. In spite of the predictability of our paradigm and the long follow-up period, multiple hypometric saccades into the blind field appeared to be the preferred strategy.

Comparison of pattern-onset, -reversal and -offset VEPs in treated amblyopia.

PURPOSE: There are differences in the properties of visual evoked potentials (VEPs) to various forms of pattern stimulation and it is not clear how these differences reflect macular and parmacular function in amblyopic and normal eyes. We assessed pattern-onset, -reversal and -offset VEPs from amblyopic eyes and compared them with the responses from the fellow eyes, and from controls, to gauge the relative effectiveness of these stimulus modes. METHODS: The three modes of pattern stimulation were presented sequentially in a single recording run to enable direct comparisons to be made for identical recording conditions. Half-field stimulation was used, as this elicits components over the ipsilateral and contralateral occipital scalp relative to the stimulated half-field, which reflect stimulation of macular and paramacular areas of the visual field. Eighteen amblyopes treated by occlusion and 20 control children were studied. RESULTS: Multivariate analysis of variance showed significant differences between ambylopic and fellow eyes in amblyopes: pattern-onset components were significantly attenuated and ipsilateral reversal components were significantly prolonged in amblyopic eyes. When fellow eyes of amblyopes were compared with the eyes of controls, the reversal P100 and offset P110 and N165 components showed significant differences. CONCLUSIONS: Ipsilateral reversal components and onset CII and contralateral P105 were the most affected in amblyopic eyes. The subnormal findings for the fellow eyes of amblyopes suggest that occlusion may have a long-standing physiological effect on the patched eye, not normally clinically apparent.

Severe microcornea with anterior segment malformation in a mother and her son.

A male infant with microcornea, anterior segment dysgenesis and congenital cataracts, but with a normal ocular posterior segment is reported. His mother also had extreme microcornea, no useful vision from birth, but had globes of grossly normal size.

Neurology of latent nystagmus.

We report eye movement findings in 30 patients with latent nystagmus and who were found to have a variety of associated oculomotor disorders. Latent nystagmus is defined clinically as nystagmus which appears on covering one eye and beats towards the uncovered eye. Recordings showed that the latent nystagmus in 28 patients had slow phases with linear or exponentially decreasing velocity. This nystagmus is termed 'LN'. In 13 of these patients certain manoeuvres (e.g. pursuit) provoked nystagmus with exponentially increasing slow phase velocities characteristic of the congenital form of nystagmus termed 'CN' and we propose that this is a forme fruste of CN. In two patients the nystagmus provoked by cover was latent CN. Twenty-nine patients had a history of strabismus and one had a marked phoria. Some patients had amblyopia whilst others had normal vision in each eye. Although binocular vision was usually absent, six patients had varying degrees of stereopsis. A temporonasal predominance of monocularly elicited optokinetic response previously associated with LN, was present only in a minority of patients. Some responses were bidirectionally absent or of low velocity, possibly the result of a cortical impairment of visual motion detection. The most deranged responses had slow phases which were in the opposite direction to the stimulus as described in CN. The presence of 'forme fruste' CN in many of these patients suggests that some of the derangements of optokinetic responses are due to CN. The findings indicate a greater overlap between the incidences of LN and CN than previously estimated. Thirty percent of patients had large saccadic 'square wave' intrusions. These were not present when there was marked amblyopia. They are attributed to a competitive incongruence of visual fields and eye positions. Dissociations found between the presence and severity of strabismus, stereopsis, amblyopia and optokinetic abnormalities point to these features being relatively independent although associated in typical clusterings. This is evidence against the theory that strabismus and LN are directly caused by nasotemporal optokinetic imbalance which persists because of failure to develop binocular vision. The variability of findings favours the view that LN and CN arise from a genetic or acquired embryological disorder with various degrees and directions of expression.

Clinical evidence for the onset of the sensitive period in infancy.

Seven neonates had a IIIrd or VIth nerve palsy or afferent visual pathway pathology at birth. These abnormalities resolved within 6 weeks and the children have developed normal visual acuity, motor fusion, and stereopsis. We conclude that there is a latent period of 6 weeks before the onset of the sensitive period.

The toxicity of purified cellulose in studies with laboratory animals.

The available literature has been reviewed for studies in laboratory animals using purified cellulose, as the production of purified cellulose may result in trace organochlorine contamination. The chronic ingestion of purified cellulose over the entire lifespans in rats and mice does not result in any increase in spontaneous disease or neoplasia. Further, purified cellulose does not display promotional activity in the mammary gland, the colon, or the bladder of rats and does not significantly alter the absorption or the metabolism of dietary components. No adverse effects were found on reproduction or neonate development in rats and mice. Therefore, no adverse health effects in humans are expected from exposure to purified cellulose.

A serological survey of rinderpest antibody in wildlife and sheep and goats in northern Tanzania.

An extensive serological survey for rinderpest antibody in wildlife, principally buffalo (Syncerus caffer), and sheep and goats has been undertaken in the previously endemic region of Northern Tanzania to determine whether or not the virus has continued to cycle in susceptible species since the last occurrence of overt disease in 1982. The results show that infection but not disease has occurred at least until 1987 in buffalo in parts of the Serengeti National Park but not in the other game areas of Tanzania where samples were taken. Sero-positive sheep and goats were widely distributed and have been found in 10 of the 14 districts sampled but there have been no reports of disease. These findings bring into question the possibility of eradicating the disease from Africa and continuous annual monitoring of this and other similar ecological zones will be required.

Oculokinetic perimetry for the assessment of visual fields.

The visual fields of 13 children aged 7 to 16 (mean 10.7 years) were assessed by oculokinetic perimetry (OKP), a technique where the field of vision is tested at reading distance using a simple chart, and the results compared with conventional Goldmann perimetry. Cooperation with testing was greater for OKP than Goldmann perimetry and in some cases OKP was better correlated with clinical findings. The advantages of visual field assessment by OKP for children are the close proximity of observer and child, the absence of the requirement for prolonged fixation, and the inexpensiveness and portability of the testing equipment. The disadvantages are movements of the head, with variability in the distance from the target, and the limitation to the central 25 degrees of the visual field.

Visual evoked potentials in dissociated vertical deviation: a reappraisal.

Pattern reversal and flash evoked potentials were recorded in 13 children with dissociated vertical deviation (DVD). No electrophysiological evidence was found to support the notion that patients with DVD have an anomalous (albinoid) projection of visual fibres originating from the temporal retina of each eye. However, DVD patients had significantly smaller monocular and binocular pattern evoked responses than age matched controls. Explanations are given for this finding and for the occipital VEP asymmetries reported by other workers.

Microsomal and cytosolic epoxide hydrolases, the peroxisomal fatty acid beta-oxidation system and catalase. Activities, distribution and induction in rat liver parenchymal and non-parenchymal cells.

A number of structurally unrelated hypolipidaemic agents and certain phthalate-ester plasticizers induce hepatomegaly and proliferation of peroxisomes in rodent liver, but there is relatively limited data regarding the specific effects of these drugs on liver non-parenchymal cells. In the present study, liver parenchymal, Kupffer and endothelial cells from untreated and fenofibrate-fed rats were isolated and the activities of two enzymes associated with peroxisomes (catalase and the peroxisomal fatty acid beta-oxidation system) as well as cytosolic and microsomal epoxide hydrolase were measured. Microsomal epoxide hydrolase, cytosolic epoxide hydrolase and catalase activities were 7-12-fold higher in parenchymal cells than in Kupffer or endothelial cells from untreated rats; the peroxisomal fatty acid beta-oxidation activity was only detected in parenchymal cells. Fenofibrate increased catalase, cytosolic epoxide hydrolase and peroxisomal fatty acid beta-oxidation activities in parenchymal cells by about 1.5-, 3.5- and 20-fold, respectively. The induction of catalase (2-3-fold) and cytosolic epoxide hydrolase (3-5-fold) was also observed in Kupffer and endothelial cells; furthermore, a low peroxisomal fatty acid beta-oxidation activity was detected in endothelial cells. Morphological examination by electron microscopy showed that peroxisomes were confined to liver parenchymal cells in untreated animals, but could also be observed in endothelial cells after administration of fenofibrate.

Pattern- and flash-evoked potentials in patients with dissociated vertical deviation.

Pattern reversal and flash evoked potentials were recorded in 13 children with dissociated vertical deviation. We found no evidence of anomalous responses to pattern reversal half-field stimulation and no asymmetries in flash responses as reported to occur in albinism. However, we found that patients with dissociated vertical deviation had significantly smaller monocular and binocular pattern responses compared to a group of age-matched control subjects.

Time-dependence and differential induction of rat and guinea pig peroxisomal beta-oxidation, palmitoyl-CoA hydrolase, cytosolic and microsomal epoxide hydrolase after treatment with hypolipidemic drugs.

Fischer-344 rats and Hartley guinea pigs received a diet containing 0.01% (w/w), 0.05% (w/w), or 0.25% (w/w) of the hypolipidemic drug fenofibrate. Rats were treated for 4, 7, 14, or 21 days, and a clear dose-dependent and weak time-dependent increase in liver/body weight ratio was observed. The specific activity of peroxisomal beta-oxidation increased linearly with time at all concentrations used. A dose-dependent increase in cEH was observed, but the activity remained constant after treatment for 7 days. Enhancement of palmitoyl-CoA hydrolase was dose-dependent, but was similar at all 4 time points investigated. In contrast to the other enzyme activities, mEH was not or only minimally (less than 1.5-fold) induced. In contrast to the rat, treatment of guinea pigs with fenofibrate for 1 week did not change liver weight or enzyme activities. Prolonged treatment of guinea pigs (4 weeks) with fenofibrate did not result in an increase in enzyme activities. This was also observed with clofibrate whereas tiadenol caused a slight increase in enzyme activities (1.5- to 2.6-fold). In contrast to the guinea pig each of the three hypolipidemic drugs led to an increase in enzyme activities in the rat liver after treatment for 1 week.