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Delayed visual maturation: an update Isabelle Russell-Eggitt; C M Harris; A Kriss; Great Ormond Street Hospital for Children NHS Trust, London, UK. l'he term 'delayed visual maturation' (DVM) can he applied either in a broad sense to all infants who appear to be blind yct subsequently dcvelop some vision, or, more specifically, t o a group with normal ocular and systemic clinical examination whose visual behaviour markedly improves by 4 to 6 months o f age and whose visual acuity is subsequently normal. The term DVM is used both as a diagnostic label in this latter group (as there is no more specific diagnosis) or as a descriptive term of a behavioural phc'nomenon in its broad definition. Without a consensus on usage there is therefore some confusion in the literature. Those who favour the broad approach subclassify DVM into type 1. which cocrcsponds to the latter specific group; type 2, in which there is neurological abnormality and/or learning disability and in which visual knction is often, but not invariably, permanently impaired to some degree; and t y p 3, where there is an ocular abnormality and nystagmus develops with visual improvement (Uemera et al. 1981). Fieldcr and Mayer (1'991) further expanded the classification by limiting type 5 to albinism and idiopathic congenital nystagmus, and separating severe ocular disorders into type 4. In all types of DVM the diagnosis can only be confirmed retrwpectively. 'The pathophysiologyof DVM is not h o w n and it is likely that avariety of neurological insults may manifest similarlyasvisual inattention in infanq. Even DVM type 1 may not be a single entity. Field& et al. (1985) divided type 1 into s u b types A and B dependent on the absence or presence of perinatal problems. We have adopted the 'splitting' philosophy, studying primarily the more well-defined DVM type 1 , but we have found [he margins between types 1 and 2 blurrcd and recognise tht: possibility that a spectrum may exist. Whilst the 'lumping' approach has the attraction that a common thread can be sought, this rather makes. the assumption that the underlying pathophysiology is uniform. One example which demonstrates that distinct disorders may present similarly to DVM is that of intermittent horizontal saccade failure (congenital oculomotcirapraxia). in which an infant appears blind until head-thrusting and/or synkinetic blinks develop. In the broad use of the term, 'DVM'would apply. We suggest that, where a more precise diagnostic label can be applied, 'DVM' should not be used; the term should be reserved for the more spec!fc but as yet unexplained group. Is there any merit in classifyingblind infants with albinism as having 'type 3 DVM' rather than just noting that early visual inattention is a feature ofalbinism (Nettleship 1907)? Beauview (1926, 1947) first used the term 'temporary visual inattention' to describe blind infants with subsequent 130 DevelopmetttalhfedicitaeGChildNeitrology 1998,40: 130-136 vision. This is probably a more appropriate term than 'delayed visual maturation' later coined by Illingworth in 19619as there is evidence that the primary visual pathway is well developed in spite ofapparently blind bchaviour. Clinical picture of type 1 DVM PRESENTATION AND OClILAR.F.XAMINA'I7ON Type 1 DVM is uncomplicated by signs ofother ocular or neurologic pathology. Initially the infant is behaviourally blind and will not reliably fixate or follow a light or a large bright objcct. No visual response will be obtained on behavioural tests of visual acuity, such as the use of preferential looking cards. The eyes may be divergent (less commonly they are convergent) or 'roving'. Pupil reactions to light arc normal. Ocular examination is normal,'except for a few cases where a grey coloration of the optic disc is noted at presentation (kauvieux 1947, Law 1961, personal observation). \III.ES'I'ONES The onset of smiling is usually delayed t o the age of 8 w e e k or later, and is commonly prompted by handling or a voice. Fielder et al. (1985) reported that an apparent delay in hearing (orientation to sound) may occasionally be associated with DVM. Illingworth (1061) noted that one child in his study was 9 late walker. Hoyt et al. (1983) reported general motor delay in sevcn of eight patients. Cole et al. (1984) noted that a proportion were slow to speak. Lambert et al. (1989) reported that four of nine children were delayed intheir motor milestones (sitting and walking) by 3 to 5 months of age. However, on follow-up not all of their cases could be classified as type 1. It became apparent that one patient was globally delayed by the time 3 years of age had been reached, and although a C'r scan in infancy was reported as being normal, an MRI scan of the brain at subsequent follow-up demonstrated cortical atrophy and lesions in the thalamus. Mild to moderate delayed motor milestones and delayed development of expressive specch arc also common features o f 'ocular motor apraxia' (Harris et al. 1996a). A further infant who was in the ~ p l egroup in Lamben's papersubsequently developed a seizure disorder. Generally, if apparent blindness is the sole presenting feature the neurodevelopmental outlook is good. It appears that delay in spheres other than vision carries a poorer neurological prognosis. ELECTROPHYSIOI.O(~I(:Al.FINDIN(;S There is general agreement among studies that the flash electroretinogram (ERG) is normal in type 1 DVM (Mellor and Fielder 1980, Harel et al. 1983, Hoyt et al. 1983, Fielder et al. 1985, Lambert et al. 1989). . However, there is controversy as to whether the visually evoked potential is altered in DVM. It is important to interpret infant visual evoked potential (VEP) data with reference to age-matched control norms. Mellor and Fielder (1980) rebrted.that the flash VEP was abnormal during the blind phase of DVM type 1. In one casc the VEP was absent; in the remaining three cases it was felt that the waveform was immature and subsequently became normal. Harel et al. (1983) agreed that the waveform was abnormal, felt the latency was prolonged, and noted that the VEP was subsequently normal. Unlike Mellor and Fielder (1980) they did not commcnt on the normal maturational changes of thc VEE Fielder et al. (1985) in a further study reported the findings in 15 type 1A infants (a more rigorous definition of type 1 from which infants with known perinatal insults were excluded). In three of 15. cases the VEP was normal. However, in'nine of the 15 there was 'persistence of simple neonatal waveform' and/or reduced amplitude, and in ten cases there was delay of the P2 component of the VEE They combined the rcsults from three laboratories, which did not all use identical equipment. N o mcthodological details were given conccrning electrode .positioning and derivation (which mainly ects response morphology and amplitude), background illu ination (which affects the degree of rod and cone functio ), or attentive state of the infants (eyelid position and arousal affect both the amplitude and lateficyof ERGS and VEPs). Although in the discussion section of Fielder et al. (1985) thcre is a reference to the considerable VEP variation and age-related latency changes reported by Fielder et al. (1983), there is n o indication in the later paper of what criteria were used to identi@ VEP components, and whcther components were compared with age-matched contra1 data. Lanjbert ct al. (1989) reported on pattern-reversal VEPs (pVEP) to 100-min checks, and flash ERGselicited underscotopic conditions wtye recordcd from nine infants with type 1 DVM (later revised to type 2 in two of the nine cases).It is well established that pVEPs provide a more reliable assessment of visual function compared with flash VEPs (Halliday 1993). VEPs were recorded at O z (about 3cm above thc inion) using a midfrontal reference (Fz). Infants were alert and their fixation was monitored throughout. The ERG and VEP responses were compared with those of age-matched control infants. There were n o significant group differences in pVEPs and flash ERGS when comparing DVM patients and controls. Two of the possible explanations for this discrepancy are as follows. (1) Even DVM'type 1 may not have a single cause, and in some cases the generators of the VEP may be abnormal and in others the lesion may be elsewhere. It is interesting to note that in a study which compared the flash VEP o f normal preterm infants with that of infants with neonatal periventricular haemorrhage, the latter group had immature and delayed waveforms (Dubovitz et al. (1986). By the time an infant is investigated for apparent blindness, periventricular haemorrhage (which may occur in term infants, albeit less commonly than in preterm births) has resolved. Could those infants with abnormal VEP in DVM have had periventricular haemorrhage? Does the finding of an immature flash VEP carry a different prognosis? ( 2 ) There is wide variation in the 7 normal waveform even in the visually 'attentive normal infant. It is therefore verydiflicult to establish what is outside the normal range. If agreement cannot be reached about the flash VEP in DVM type 1 it is not surprising that there are differences of opinion on the pVEP when thcre is much more variation in stimulus and laboratory methodology. In all eight of Mellor and Fielder's (1980) cases the VEP to pattern onset-offset was absent or significantly attenuated. l m b e r t et al. (1989) studied nine infants with DVM and found that, when compared with age-matched controls, not only the flash VEPs but. also the pattern-reversal VEPs to moderate-sized checks (100 min) were normal. OCULOMOTOR FINDINGS Although it is not characteristic of type 1 DVM, transicnt nystagmus has been reported: two of 20 cases (Ficlder et al. 1985) one case associated with intra4entricular haemorrhagc; and two of 16 (Cole et al. 1981). Recordings in our eye movement laboratory to date have shown that although the DVM infant does not voluntarily tix and follow, biocular full-field optokinetic nystagmus (OW) can be readily elicited (Harris et al. 1996b)..Thus it appears that the brain stem saccadic mechanisms are functional. However, monocular OKN. is markedly asymmetrical with virtually no na5otemporal following, which is a more immature state than that of age-matched controls (limben et al. 1989). These data indicate that cortical inadequacies may be involved in DVM (see Pathophysiology of DVM, below). When fiving and following become apparent, smooth pursuit and saccades can be elicited. Visual orientation improves, often rapidly over 1 or 2 weeks, betwcen 3 and 5 months ofage. Initially saccades are hypometric and smooth pursuit saccadic; monocular OKN remains asymmetrical. Usually ovcr the next few months completely normal eye movement recordings are attaiped. Monocular OKN becomes symmetrical, provided strabismus does not devel-op. At this age there is considerable variation in normal subjects, so a larger study group and longer follow-up will be needed before a prognostic significance can be assigned to any residual abnormalities detccted by cye movement recording, but it appears that persistence of,abnomal eye movement recordings may correlate with neurological dcficit (personal observation). The vestibulo-ocular response is recordable at all stages in infants with DVM type 1. Hoyt tested for vestibulo-ocular response by observing the infant's cyes while holding the child and spinning with himself as the centre of rotation (Hoyt et al. 1983). In six of eight infants a lack of the normal fast phase was noted; the eyes just deviated to the side opposite to the direction of spin. This pattern has been described in normal preterm infants (Eviatar ct al. 1971), and it is relevant to note that several of his subjects were preterm or small fordates. Ocular motor apraxia was not specificallyexcluded in their group of patients. If this 'lock-up' behaviour on spinning is observed in an infant with a comcted age of at least 1 month, we would be concerncd that the child may have a form of intermittent saccade failure (ocular motor apraxia) with a possible neurological deficit. In these patients visual behaviour is likely to improve, placing them in the DVM type 2 category. It is relevant to note that one patient of the nine in the study by Lambert et al. (1989) had absence of saccades on - Annotation 131 spinning and also in response to an OKN drum; this abnormality persisted and lesions in the thalamus were noted on MRI scan. In the absence of prematurity, lack of nystagmus induced by spinning the infant should alert the clinician to the presence of neurological deficit other than DVM type 1. It is 'important to note that ;ihandheld OKN tape o r O W drum is likely to elicit a pursuit response rather than the true OKN obtained when using a large field stimulus. This explains the absence of response to these stimuli by DVM infants reported by Cole et al. (1984), while we observe the full-field OKN responst: to be intact in DVM at all stages. should be considered as a factor leading to poor visual attentiveness in infants predisposed to seizures. If there hasbeen no improvement in visual responsiveness by 6 months of age (corrected for any prematurity) then the diagnosis is not likely to be DVM type 1. Most DVM infant.. show a marked improvement in vision between 3 and 4 months of age. The 6-month-old baby who appears blind (and who has a normal ERG and age-matched VEP) may yet achieve good vision, but is more likely to have a significant persistent neurological deficit. By definition, all patients with type 1 DVM achieve normal vision. Although all the abov? clinical information is helpful in the prediction of outcome, definitive classification into type is done retrospectively. NEI!W~IMM;ING Lambert et al. (1989) reported a normal CT scan of the brain in the four cases in their study where ncuroimaging was performed. However, one of these four patients subsequently had an abnormal MRI scan. Boltshauser et al. (1992) reported a heterogeneous series of children with poor visual behaviour. In those who may have been classified as DVM, either the imaging was normal or a variety of abnormalities were found, there being no consistent pattern associated with DVM type 1. In a study of 14 infants with type 1 DVM, H o p and Good (1993) found no specific pattern ofmyelination abnormality, a delaycd pattern bcing found in only three caws. Oh11 O O K W R DVM TYPE 1 I All I6 babies in Cole's study developed visually attentive behaviour between 4 and 6 months o f age and had normal or nearly normal 'acuity' (by Catford drum) by 1 year of age (Cole et al. 1984). Fielder et al. (1985) divided DVM type 1 into lA, with unremarkable perinatal history, and l B , with known perinatal insult. The median age of visual improvement (a qualitative judgement) for 42 infants with type I DVM was lkvceks (range, 9 to 18wcek\ for type lA, 1 1 to 40 week.. for type 1B). Tresiddcr et at. (lY10) reported that seven of eight infants with type 1 achieved normal acuity between 12 and 17 weeks of age, as assessed quantitatively by preferential looking techniques. Visual behaviour appeared to be normal by 26 to 44 weeks of age in the paper by H o p et al. (1983). The apparentlyslowerdevelopment in Hoyt's study may in part be due to inclusion of preterm infants, infants who were small for dates, and those with perinatal.problems. Ages given were not corrected for postmenstrud age and visual behaviour; for example, smiling to a visual stimulus is later in onset in preterm infants with no other problems. If the eyes are convergent at presentation then the squint is likely to persist and may be associated with perinatal neurological insult and a low o r low normal developmental quotient (Cole et al. 1984, Fielder and Mayer 1991). However, infants who have divergent eyes at presentation , (the commoner finding) are expected to have straight eyes with steady- tixation when visual behaviour improves (Fielder et al. 1985). Moderate general developmental delay may be seen in a minbrity of cases o i b V M type 1. Two of sixteen cases in the seriesof Cole et al. (1984) developed epilepsy and one of the nine in the series ofLambert et al. (1989) had a seizure disorder. Both uncontrolled seizures and anticonvulsant therapy can affect gtperal alertness, including visual behaviour, and 132 DevPCopmentalMedicitteCChildNeurology 1038,40: 13G136 Type 2 DVM Patients with'DVM type 2 show a slower and often incomplete visual improvement compared with patients with DVM type 1. The clinical picture in DVM type 2 is more complex and the underlying mechanisms are possibly different. Infants classified asDVM type 2 have significant neurological abnormalities on neuroimaging and are likely to have impairment of full-field OKN. Many affected infants have had perinatal (often hypoxic) damage, which probably affects the extrageniculostriate visual system to a significant extent. It has been suggested by several author3 that this extrageniculate system matures early or predominates in the very young infant, and as the geniculostriate system develops visual performance improves (Bronsyn 1974, Atkinson 1984, Dubovitz et al. 1986, Fielder and Evans 1988). kc we find full-fieldOKN to be normal in infants with good global outcome (DVM type 1) and to be abnormal in those with neurological damage (group 3 in Shawkat et al. 1996), the eye movement recordings may bl- of some prognostic significance. However, in our experience not all cases with full-field bi-ocular OKN at presentation have good global outcome. If nystagmus is present when visual behaviour is poor then a'neurological cause such as intraventricutar haemorrhage or raised intracranial pressure should be sought. An infant with Lebcr's congenital amaurosis often will have roving eye movements rather than nystagmus; however, it may be difficult to gauge visual behaviour clinically and it is very useful to perform an electroretinogram and tlash visual evoked potential to demonstrdte the basis for the profound visual loss. In type 2 DVM, development o f vision is gndual and later than in type 1 DVM, with improvement over severd months and in some cases over years (Lambert et al. 1987). - Type 3 DVM Infants with DVM type 3 show an improvement in visual behaviour more gradually and at a slightly later age than those with DVM type 1 (median age 20 versus 14 weeks; Fielder et al. 1985), and visual acuity does not reach normal levels, bcing impaired by the associated ocular disorder. Fielder et al. (1985, 1991a) and Fielder and Evans (1988) noted that patients with DVM type 3 developed characteristic congenital nystagmus 1 or 2 weeks before behavioural improvement in vision. In most oculo-cutaneousalbinos and in some ocular albinos nystagmus may be absent when visual behaviour is poor (Fielder et al. 1985, Fielder and Mayer 1991). Initially the eyes may appear steady, but the infant does not fix or follow. In others, at presentation the eye movements may appear chaotic or roving, and in our experience infant albinos with poor futation bchaviour have had a large-amplitude horizontal pendular nystagmus with a typical triangular waveform on formal eye movement recordings (Reinecke et al. 1988).A similar waveform can occasionally be recorded from adults with congenital nystagmus if the patient is completely inattentive (Abadi and Dickinson 1986).About the time of visual recovery, nystagmus is characteristically uniplanar with slow large oscillations, movements becoming rapid and finer with age (Reinecke et al. 1988). Thus the 'roving eyes' probably represent congenital nystagmus in an infant with poor or absent attentional capability (see below). As the infant develops attentional behaviour the nystagmus may decrease in amplitude and take on a more typical appearance. " m e 4 DVM Fundoscopy and electrophysioloby are essential in helping to identify sensory defects (see Differential diagnosis of .DVM. below). In our practiccwe d o not use the terms DVM type 3 or DVM type 4. but are cautious about prcdictingvisual prognosis on the pasis o f infant visual behaviour in the presence o f sensory deficit, as this phenomenon of apparent initial blindness occurs in .very many ocular disorders, including congenital retinal dystrophies and structural abnormalities such as optic nerve hypoplasia and macular coloboma (Fielder et al. 1991b). Differential diagnosis CORTICALV I S I ~ A I I M P A I R M ~ Nr In cortical visual impairment, as the'rcsponses of the pupils and ocular examination tend to be normal there is a clinical picture similar to that of DVM,which can leadto confuFon. However, the VEP response to flash is usually abnormal and the response to pattern stimulation is attenuated and degmded (Kriss and Thompson 1996). The full-field OKN is also usually impaired (Jacobs et al. 1993). Neuroimaging is very likely to be abnormal. SACCADIC I N l l l A T I O N 1:AILIIRE (OCUI.O%4O'I'OR APRAXIA) , Congenital saccadic initiation failure (cSIF) is a condition in which there is intermittent failure of the triggering of saccades. cSlF is associated with a wide range o f neurological conditions, including CNS malformations (e.g. agenesis of the corpus callosum, cerebellar vermis dysplasia), lipid storage diseases, and various non-progressive perinatal insults, but in many caws no underlying pathology can be found (Harris et al. 1996a). In this latter form ofcSIF, which is often referred to as oculomotor apraxia, there is preservation of eye movements in the vertical plane. Thus the infant is attentive in this plane, which maybe demonstrated by testingwith' an OKN tape or drum vertically rather than horizontally. The infant cannot follow a target until there is sufficient head control to perform characteristic headthrusts, and thus may mimic DVM in earty behaviour. Adistinctive and constant feature of cSlF is the intermittent failure of the OKN quick phases that cause the eyes on O K N stimulation to deviate to the limit ofgaze ('locking up'; Cogan 1972, Harris et al. 1996a). 'fius full-field OKN can usually distinguish between cSlF and DVM. Manual spinning induces vestibular rather than optokinetic nystagmus and some normal infants will lock up at under 1 month of age. particularly if they were born prematurely. The ERG and VEP is usually normal in cSIF (Shawkat et al. 1996), as it is in DVM,but there may be an associated pigmentary retinopathy with reduced ERG when cSlF is part of a particular syndrome (e.g Joubcrt syndrome, mitochondria1 disorders). R E l I N A L DYSTROPHY (1NCI.l;IMNG LEBER'S hHAlIHOSIS) Clinically there may be confusion between DVM type 1 and retinal dystrophies such as Leber's amaurosis, in which there is a severe defect of both rods and cones, and cone dystrophy, in which there is preserved rod function but poor acuity with the cone deficit. Clinical clues that the diagnosis is not DVM type 1 are a high refractive error and abnormal pupil reactions. 'The fundus examination is often normal in infancy. An abnormal flash ERG will distinguish retinal dystrophies from DVM type 1. However. infants,with receptor dystrophy can often be considered as having Dvivl type 4 as. they may fill the criterion of presenting as blind but subsequently exhibitingsomevision (Fielder and Mayer 1991). , (ILOBAI. . DEVEL0P.W ENTAL DEIAY Visual inattention maybe the prrsentingclinical feature in an infant who is globally rctarded, for example due to a developmental cerebral defect such as lissencephaly. The VEP and ERG is often normal in lissencephaly. It could be argued that all infants with DVM should have neuroimaging at an early stage rather than only scanning those who fail to develop normal visual behaviour by 6 months of age. If this policy were to be adopted many cases would have an unnecessary scan. Abnormal gym1 formation may be accompanied by other structural malformations, including those of t k cerrbellum, and may be associated with eye movement abnormalities and an abnormal EEG (unpublished data). A$ EEG examination should therefore be considered in the investigation of the apparently blind infant. - *. EPILEPSY A N D DRU(nS 3 An infant having frequent seizures may appear to be visually unresponsive. However, the majority of infants with frequent seizures will present as initially visually alert with reduced responsiveness only at the onset of the seizures. Similarly, drugs used to treat seizure disorders may have a sedative effect and an apparent inadequate attention to visual stimuli may be misinterprged as a lack of vision, but it would be unlikely to abolish visual function altogether and so would rarely be confused with DVM. However, an EEG may occasionally be helpful in the investigation of the apparently blind infant (see below). < 3 # <)PTIC NERVE IIYPOPLASIA Optic nerve hypoplasia sufficiently severe to present as blindness can usually be diagnosed on fundoscopy. However, ii can occasionally be missed if [lie clinician is not carefully looking for optic nerve hypoplasia and if the examination of the infant is difficult, particularlywith the reduced magnification of a high-power c o n d e n h g lens and an indirect rather than a dirkct ophthalmoscope. However, the flash VEP will be markedly attenuated or nondetectable'and the flash ERG will be of normal or larger than nprmal size. As with retinal dystrophy, some uxful vision can develop in infants apparently presentingwith no perception of light. Annotation 133 C O C A I N E EXPOSUHE Good et al. (1992) described 13 cocaine-exposed infants with'optic nerve abnormalities, delayed visual maturation, and prolonged eyelid oedema. He advised that infants with any of these eye abnormalities be carefully investigated for cocaine abuse. DVM was only diagnosed if the infant was still unresponsive at 2 months of age, and of the seven infants with DVM only one had unilateral optic nerve hypoplasia. DVM appears to be a feature ofcocaine exposure rather than being due to an.ocular defect. A l l IlShl Generally DVM children d o not develop autism and autistic children d o not usually have a history of DVM. Autistic children may display abnormal visual behdviour. fixating inanimate objects while ignoringpeople, but this behaviour does nbt mimic blindness. However, although not a frequent finding. DVM may coexist with autism. 'DVM' has been reported in three children in whom thc'diagnosis was subsequently revised to autism (Goodman and Ashby 1990). All three appeared to have very poor vision in the first year; subsequently two developed nystagmus and esotropia and the third oculomotor apraxia. Visual behaviour improved by 7 to 12 months ofage. Aetiology of DVM PEHINATAI.lIYYOXIC/HAEMORHHA~~I(~ I N S l i l T S O H ( ; N 5 S'I'HI!(:IUHAI. ANOMALY In Hoyt et al. (1983), six of eight patients were preterm or small for dates. llowever, other authors report a much lower incidence of prematurity (three of eight in group 1A of Tresiddcret al. 1990).All nine infants in the study by Lamhen ct al. (1989) were term. Most studies into the aetiology,of DVM take care to exclude infants with known perinatal problems such as kypoxia and periventricular haemorrhage. However, even apparently well infants may have suffered some mild perinatal neurological damage. Are DVM types 1 and 2 just two ends of a spectrum? Fielder (1985) proposed that a proportion of his patients with type 1 DVM may have had minimal brain damage. On further investigation of this cohort, ,six of 16 of the infants initially classified as type 1A DVM were tliscovered to have had perinatal problems and three others had developed sequelar (one mild hemiplegia and two strabismus] (Tressider et al. 1990). Areis of the brain vital for normal fixing-and-following behaviour of infants may be especially sensitive to insult or may be structurally abnormal. Hoyt and Good (1993) reported that five of 14 patients with a clinical diagnosis of type 1 DVM after ocular and neuI rology examination actually had structural abnormalities of various parts of the visual and motor areas on MKI scanning. There is a significant prevalence of mild to moderate developmental delay o n long-term follow-up of infants with type 1 DVM, which implies either minimal brain damage or subtle structural anomaly. ' Pathophysiologyof DVM In order to formulate a hypothesis as to the pathophysiology of DVM we have to ask what are the steps in the generation of a normal infant's response to a visual target? A visual object produces a focused image on the retina, and a'signal (electrical representation of both target and background) is 134 DeueloprnentalMedicine & ChildNeurology 1398.40 130-136 transmitted by the visual pathways to the visual areas of the brain. For this td elicit a response the infant has to recognise this as an object of interest distinct from the visual background. The infant needs toattend to the target. lfthe object is perceived and stimulates interest then the motor pathways have to be functional to produce a motor response. In principle, DVM type 1could bedue to asensory, attentional, or motor defect. RE'I'I N AI. I M MAIU RI'IY Visual behaviout in DVM is too poor to be explained by a foveal abnormality with peripheral retina functional (Mellor and Fielder 1980). A general retinal immaturity appears not to be the cause of DVM as it is generally agreed that the flash ERG is normal for age (see above, Electrophysiological findings). DELAY IN hlYELINATION Myelination is not fully complete at term, and increases in the anterior visual pathways over the first 2 years of life. Beauvieux (1947) tlcschbed the optic disc a s appearing slate-grey but later becoming normal in appearance, and vision improving over a similar time course. This appearance is o n occasion quite dramatic but is certainly not a consistent finding. Sokol and Jones (1979) demonstrated that the maturation of the latency of the visually evoked potential .occurs rapidly between 3 and 5 months. Although a delay in myelination could theoretically be a component in DVM it could not explain the dramatic bchavioural improvement, as even during the behaviourally blind phase pVEP recordings may be not significantly different from those of age-matched controls (tambert et al. 1989). Hoyt and Good (1093) reported delay in cerebral myelination on MKI scan in only three of 14 patients with IlVM type 1. STRlXl'E COR'I'EX As pVEPs are believed to arise in the striate cortex and have been reported to be normal for age in DVM typc 1, an abnormality in this site is unlikely to be responsible for the blind behaviour (Lambert et al. 1989). It is not known to what cxtent the striate cortex is important in normal infant visual responses. I t has been suggested that normal infant vision is predominantly extragcniculostriate (colliculus-pulvinar-parietal) (Fielder and Evans 1988). If this is true for the normal infant then an abnormalityof the . striate cortex cannot be the prime cause of behavioural , blindness inDVM. 'IHAIA,MLIS A N D DOHSAI. BRAIN S'I'Ebl ! Dubowitz et al. (1986) reported that lesions f the thalamus are more likely to affect the visual behaviou of infants than lesions of the visual cortex. Thc thalamus a d dorsal brain1 stein may be particularly vulnerable to damage by perinatal hypoxia. There is no strong evidence for this mechanism in DVM. The presence of a VEP normal for the patient's age implies a functioning lateral geniculate body. Vertical eye movement defects are a common manifestation of thalamic disease and are not'sclectively affected in DVM. The pathways for cortically mediated OKN are thought to descend via the pulvinar, so that as full-field OKN is preserved a postulated thalamic lesion would have to be rather selective. , A tten tional defect References FRONTAL O R PAHIEIAI. CEREBRAL CORTEX Abadi RY Dickinson CM. (1986) Waveform'chardctcristics in congenital nystagmus. Doclimetila Ophthalniologica 64: 153-67. AtkinsonJ. (1984) Human visual development over the tirst 6 m ~ n t h of s life.A review and hypothesis. HiinranNeiirobiology 3~61-74. BcauvieuxJ. (1926) La pscudo-atrophie optique des nouveau':nCs (dysgenesie myelinique des voics optiques). Annnles d 'Vcrtlistiqiie 183:88 1-92 1. (1947) La ckcitk apparente chez Ie nouveau-ne: la pseudoatrophie grisc du nerve optiqur. Archiiwsof O p b t b a l ~ t r o l o7:~ 24 1-9. Bolthauser E, Steinlin hl. Ihun-Hohenstcin L, Banziger 0.Penoli y hlartin E. (1'992) Bildgebcnde Untersuchungen des Gehirns h i ' blinden und sehbehindcnen Kleinkindcm. !Diagnostic imaging o f the brain of blind and visually handicapped youngchildren]. KIiriiscbe~~tonatsblatferjiir Ati~etiheilkiorde200 62G2. ! Bronson G . (1974 l h e postnatal growth of visual capacity. Child Developnrent 4 5 873-90. ' C o p n DG. (1972) Heredity of congenital ocular motor apraxia. Transactions of the Anrericati Academy of Ophthulnrology and Otolarpgology 76 60-3. Cole CF, Hungerford J. Jones RB. (1984) Delayed visual maturation. Archives ofDisease in Cbikibood 5 9 107- 10. 1)ubovje LMS,MushinJ , l)e Vries f Arden GB.(1986) Visual function in the newborn infant: is it conically mediated?Luncet 1: 1 1 3 9 4 1. Eviatar L. Eviatar A. Nany 1. (197i) Matuntion of neurovestibular responws in infann. ~ei~e~opinetrlrrl Aledicitrearrd'C~Jilrl Neirrology 16:435-46. Fielder AR. Evans NM. (1988) I s the geniculostriate syst-a prerequisite for nystagmus? Ej-e2: 628-35. -hlaycr Dl.. (1991) Delayed visual inatuntion. Swiitmrs in O p h l b d ~ ?6~182-93. ~ l ~ ~ - Harper IMN! HigKinsJE, ClarkeChl, Corrigan I). (1983) The reliability of VEP in infancy.~ p ~ ~ t ~ ~faediutrics ~ ~ l i t r and ic Cerretics 3: 73-82. - Russell-Eggitt IM. Dodtls KL, Mellor DH. (1985) Delayed visual maturation. Transacf iorrs ofthe ~ J p b l b n ~ ~ ~ r o ~Society o g i c ao~j f b e United Kingdonr 104: 653-6 1.. -hlayer DL. Fulton AB. (19913) 1)elayed visual matuntion . Lance1 337 1350. (Letter.) - Fulron AB. hlaycr I X . ( 1991b) The visual development of infants with scverc ocular disordrrs. ~ ~ p ~ ~ t / ~ ~ i ~ 1t306-9. tr~~og]~98: Good NV, Ferricro DM. Golabi hl, Koori JA. (1992) Abnormalities o f the visual system in infants exposed to coainc. Opl~thnlitrolo~)~ Dendritic growth and synapse formation in the cerebral cortex begins at 25/40 gestation and is very active around birth, continuing for about 2 years. Fielder et al. (1985) suggested that eyen patients with DVM type 1, without overt perinatal probiems, may in many caws have mild brain damage. MRl studies have indicated that there may be changys in some cases but not in a specific pattern, and the scan is normal in others. We cannot be sure that there are no subresolutional changes. These may be in areas concerned with the generation of eye movements: frontal or parietal regions are goodcandidates. Harris et al. (1996b) have argued that DVM may represent a delayed development of the ability to distinguish visual objects from their visual background. Such a deficit could occur because of an inability to detect an object or i n inability to orient (attend to) an object. These authors have argued for an abnormality in the intracortical pathways, including the parietal cortex, rather than in t,he collicul+pulvinarparietal pathway. N l i l l R O i R A N S M l l T E R AUNOHhtAI.IIY I N T H E CORI1-:X Abnormal function of the cortex may be due to neurotransmitter imbalance rather than, or i? addition to, a defect in synapse formation or in myelination. Good et al. (1992) suggested that cocaine may damage dopaminergic neurones and lead to dysfunction and DVM in infants born to mothers taking cocaine. The cocaine may cause damage t o dopamine ncurones. We suggest that the parietal cortex may be particularly susceptible to intrauterine catecholarnine changes. and that this is the a r a important for visual attention. Conclusions ERG/I.'EP and eye movement studies indicate that the abnormalities underlying DVM d o not appear to be purely sensory or motor. 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