Download Delayed visual maturation: an update

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
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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
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birth, continuing for about 2 years. Fielder et al. (1985) suggested that eyen patients with DVM type 1, without overt
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Harris et al. (1996b) have argued that DVM may represent
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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
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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. Rather, it appears'that there may be a higher cortical, attcntional deficit closely linked with parietal lobe function. This may be due t o a variety of lcsions affecting parietal
function. I t may be that early visual experience, normal or
' abnormal, can influence eye-movement maturation.
DVM is not a single diagnostic condition but rather a sign
common t o neurological dmormalities affecting several
areas of the brain. In a few cases there may be delay in cortical
myelination while in others there may be a discrete structural defect which impinges on parietal cortex function.
Acceptedfor prtblicatioii 12th Arigtcst 1997.
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