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Transcript of Brain 1999 Hadders Algra 727 40
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Brain(1999), 122, 727740
Periventricular leucomalacia and preterm birth havedifferent detrimental effects on postural
adjustmentsMijna Hadders-Algra,1,2,3 Eva Brogren,1,2 Miriam Katz-Salamon1,2 and Hans Forssberg1,2
Departments of 1Woman and Child Health and Correspondence to: Dr Mijna Hadders-Algra, University2Neuroscience, Karolinska Institute, Stockholm, Sweden and Hospital Groningen, Developmental Neurology, CMC IV,3Department of Medical PhysiologyDevelopmental 3rd floor, Hanzeplein 1, 9713 GZ Groningen,
Neurology, University of Groningen, Groningen, The Netherlands
The Netherlands E-mail: [email protected]
SummaryPostural adjustments during sitting on a moveable
platform were assessed by means of multiple surfaceEMGs of neck, trunk and leg muscles and kinematics in
three groups of children, aged 1124
12years. The first group
consisted of 13 preterm children (born at a gestational
age of 2534 weeks), whose neonatal ultrasounds had
shown distinct lesions of the periventicular white matter
(PWM). The second group was the preterm control group,
consisting of 13 preterm children with normal neonatal
brain scans, matched to the PWM group with respect to
gestational age at birth, birth weight, sex and age of
postural assessment. The third group was formed by 13
healthy children born at term and matched to the PWM
group with respect to sex and age at examination. Inaddition to the postural assessment an age-specific
neurological examination was carried out. Three of the
Keywords: prematurity; periventricular leukomalacia; postural control; EMG; neurological development
Abbreviations: HAM hamstring muscles; NE neck extensor muscles; NF neck flexor muscles; PWM periventricular
white matter; RA rectus abdominis muscle; RF rectus femoris muscle; TE/LE thoracic and lumbar extensor muscles
IntroductionPreterm infants have a higher risk for the development ofmotor dysfunctions than babies born at term. The motor
dysfunctions range from the various forms of cerebral palsyto minor motor disabilities (Escobar et al., 1991; Ornsteinet al., 1991) which vary with age. During infancy, minordysfunctions especially are found in the regulation of muscletone (transient dystonia). The muscle tone dysregulationmainly affects the axial muscles and results in ahyperextended posture of neck and trunk (Drillien, 1972;Touwen and Hadders-Algra, 1983; De Groot et al., 1992).At school-age and during adolescence the most consistentlyreported minor dysfunctions are abnormalities in posturalcontrol and balance, co-ordination problems, and a poor
Oxford University Press 1999
children of the PWM group developed a cerebral palsy
syndrome, nine showed minor neurological dysfunctionand one child was neurologically normal. In the preterm
control group one child showed minor neurological
dysfunction, while the remaining 12 children of this group
and all children of the full-term group were neurologically
normal. The postural assessment revealed that preterm
birth was associated with two types of postural
dysfunction. One dysfunction was related to the presence
of a PWM lesion and consisted of a limited repertoire of
response variation. The other dysfunction was not related
to the presence of a PWM lesion, but to preterm birth
itself. It consisted of a change in the ability to modulate
the postural responses. Preterm children showed a higher
sensitivity to platform velocity than full-term children,and they lacked the capacity to modulate EMG amplitude
with respect to initial sitting position.
quality of gross and fine movements (Hadders-Algra et al.,1988; Largoet al., 1990, Soorani-Lunsinget al., 1993; Olse
n
et al., 1997). Pre- and perinatal brain lesions play a role inthe genesis of the major and minor motor dysfunctions, butthe relationship between the documented lesions and thefunctional outcome is not a simple one. Periventricularleukomalacia and haemorrhagic parenchymal lesions areassociated with a high risk for the development of cerebralpalsy, but not all infants with these types of brain lesion dodevelop a neurological handicap, nor can infants withoutsuch lesions be considered as free from risk for cerebralpalsy (De Vries et al., 1985; Fazzi et al., 1994; Rademakeret al., 1994). Likewise, an association has been found
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728 M. Hadders-Algraet al.
between the duration of periventricular echo densities and
the development of minor neurological dysfunction
(Jongmanset al., 1993), but children can also develop minor
motor dysfunction in the absence of abnormal ultrasound or
MRI scans of the brain (Roth et al., 1993; Weisglas-Kuperus
et al., 1994; Olse
n et al., 1997).
Deviant postural control can be considered as one of thekey dysfunctions in the major and minor motor abnormalities
of preterm children. Therefore, we decided to study the
relationship between brain lesion, neurological outcome and
postural control in children born before term age. Postural
control is a task of reputed complexity, as the nervous system
has to deal with a redundancy in degrees of freedom due to
the multitude of participating muscles and joints. Bernstein
(1935) suggested that the motor problem posed by the surplus
in degrees of freedom, can be solved by organizing motor
output with the help of synergies. These enable the nervous
system to reduce the number of afferent signals needed to
generate and guide an ongoing movement and to reduce thenumber of efferent activities involved in motor control. This
means that the brain does not need to specify each single
muscle contraction, but can have access to neuronal
representations of movements with prestructured motor
commands. The nervous system indeed organizes postural
control with the help of synergies/flexible synergies, which
can be fine-tuned to task-specific conditions (Horak and
Nashner, 1986; Keshner et al., 1988; Hirschfeld and
Forssberg, 1991; Allum et al., 1993; Macpherson, 1994).
Forssberg and Hirschfeld (1994), who studied postural
adjustments in sitting adults, formulated a functional model
on the organization of postural adjustmentsthe so-called
central pattern generator model. In general, central patterngenerator activity is used to describe the neural organization
of rhythmical movements like locomotion, respiration and
mastication. The central pattern generators refer to neural
networks co-ordinating the activity of many muscles. The
activity level in these networks is controlled by reticulospinal
neurons, whereas segmental afferent input results in
modulation of the output pattern (Grillner et al., 1995).
Essential to the central pattern generator model for postural
adjustments is its organization in two levels. The first level
is involved in the generation of the basic direction-specific
response pattern. Direction-specificity means that
perturbations inducing a forward sway of the body elicit a
response pattern in the muscles on the dorsal side of the
body, while perturbations inducing a backward body-sway
evoke responses in the ventral muscles. In sitting adults,
somatosensory information generated by pelvis rotation
triggers the activity of the direction-specific muscles. The
second level is involved in the fine-tuning of the basic
response pattern on the basis of multisensorial afferent input
from somatosensory, visual and vestibular systems. This
modulation can be achieved in various ways, for instance,
by changing the order in which the agonist muscles are
recruited (e.g. in a caudo-to-cranial sequence or in the reverse
order), by modifying the size of the muscle contraction (EMG
amplitude) or by altering the degree of antagonist activation.
In a recent series of ontogenetic studies we demonstrated
that three phases can be distinguished in the normal
development of postural adjustments during sitting (Hadders-
Algra et al., 1996a, 1998). The first phase is the primary
variability phase, which is characterized by a large variationin direction-specific postural response patterns. The variation
is especially noticeable in the combinations in which the
postural muscles are activated. During this phase, which
starts at pre-sitting age, postural adjustments cannot be
adapted to task specific conditions. At the end of the first
phase, around 910 months, the response pattern including
all direction-specific muscles (the complete pattern) is
selected, a process resulting in a decrease in response
variation. The second phase is the transient toddling phase,
which occurs between 910 months and 2123 years. It is
charaterized by an invariant use of the complete direction-
specific response patterns and a relatively high amount of
antagonist activation. These high-energy demanding postural
adjustments can be adapted to task specific conditions, such
as various sitting positions or different velocities of the
perturbation. During this phase the focus of adaptation lies
close to the support surface, i.e. it affects especially the
caudally located muscles. The third phase is the secondary
variability phase, during which the variation in the direction-
specific response patterns returns. The postural adjustments
are less energy demanding and consist of a variable activation
of agonistic and antagonistic postural muscles. Task specific
modulation is realized in a different way than during the
previous phase, as the focus of adaptation is now located in
the neck muscles. This phase starts at 21
23 years and
continues into adulthood, with further refinements in
adaptational abilities occurring with increasing age (cf. Berger
et al., 1985, 1995).
In the present study we assessed postural adjustments
during sitting on a moveable platform in three groups of
children, aged 112412 years: a group of preterms, whose
neonatal ultrasound scans of the brain showed distinct
periventricular white matter (PWM) pathology, a group of
preterms with normal ultrasound brain-scans and a group of
healthy children born at term. The following questions were
addressed. (i) Do PWM lesions result in (a) an absence of
the direction-specificity of postural adjustments or, in case
direction-specific postural adjustments are present, adominance of the response pattern, in which all direction-
specific muscles participate (the complete response pattern),
beyond the age of 2123 years, (b) an increased activation of
antagonist muscles as a simple solution to cope with postural
instability, (c) a delayed activation of the postural muscles,
and (d) a deficit in the ability to modulate the EMG amplitude
of the postural muscles? (ii) Do the abnormalities in postural
adjustments during platform perturbations correlate better
with findings at the neurological examination than with the
site or the size of the PWM lesions? (iii) Does preterm birth
itself affect the development of postural adjustments?
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Postural adjustments in preterm children 729
Table 1 Characteristics of preterm infants
With brain lesions Without brain lesionsPWM group PT control group
Age at assessment (years) 1.54.5 (median 3) 1.54.5 (median 3)Sex (M/F) 9/4 9/4
Gestational age at birth (weeks) 2534 (median 28) 2534 (median 28)Birthweight* (g) 7071463 (median 977) 7801135 (median 1135)Small-for-gestational age (n) 2 2Respiratory distress syndrome* (n) 8 4
*MannWhitney: no significant difference between the two groups.
Methods
SubjectsThree groups of 13 children, with ages varying from 1124
12
years, were assessed: two groups of preterm children and
one group of children born at term. The preterm children
were members of the Stockholm Neonatal Project, in which
series of infants with a birthweight 1500 g were admitted
to the neonatal unit of the Karolinska Hospital in Stockholm
during the period September 1988 to February 1993
(Lagercrantz et al., 1997). We selected from this series all
surviving children with distinct PWM lesions on the serial
neonatal ultrasound scans of the brain (Hesser et al., 1997).
This resulted in a study group of 13 children (PWM group),
whose ultrasounds either showed PWM lesions graded as
W3 (periventricular cyst formation, irrespective of the
appearance of the initial white matter echo densities) or W4
[large, intense echo densities extending into the deep layers
of the white matterincluding cases which in the Papile
classification system (Papile et al., 1978) would have been
categorized as grade IV haemorrhages]. Seven children of
the PWM group exhibited signs of haemorrhages in the
periventricular germinal matrix and in the ventricles (Table
2). For each PWM child we selected two control subjects:
(i) a preterm control from the Karolinska cohort with a
normal neonatal ultrasound scan of the brain, who was
matched to the PWM child with respect to gestational age at
birth, birthweight, sex and age at follow-up (pre-term control
group), and (ii) a healthy full-term child, matched to the
PWM child for sex and age at follow-up (full-term group).
Details on the characteristics of the preterm children are
listed in Table 1.
The children born at term were recruited amongst
acquaintances of the investigators. They had a birthweightwhich was appropriate for their gestational age and they
were free from developmental dysfunction. All parents gave
informed consent and the procedures were approved by the
medical ethical committee of the Karolinska Hospital. Prior
to each assessment on the platform, one of the investigators
(M.H.A.), who was blind with respect to the group
membership of the children, assessed neuromotor
development by means of Hempels examination technique
(Hempel, 1993). This examination technique is largely based
on a standardized, free field observation of spontaneous
motor behaviour and pays special attention to the presence
of minor neurological dysfunction. We also recorded the
body length and body weight of the children.
Experimental designThe protocol, recording and analyses techniques were similar
to those described in Hadders-Algra et al. (1996a). The
procedures were as follows.
ProtocolThe children sat on a moveable flat platform, which produced
a standard series of 32 random forward and backward
translations with an amplitude of 6 cm. It turned out that one
child was unable to sit independently. He was supported by
the experimenter. Shortly before the trial the support was
withdrawn, ensuring that the child was freely sitting during
the perturbation. Immediately after the trial, his support was
re-established. The support-withdrawal-support procedure
was also used in the study of non-sitting infants and turned
out to produce a body-sway in the direction opposite to the
platform translation (Hadders-Algraet al.,1996a). A standard
block of trials consisted of 16 slow perturbations (forward:
120 mm/s, 500 ms duration; backward: 180 mm/s, 333 ms
duration), followed by 16 fast ones (forward: 180 mm/s, 333
ms duration; backward: 220 mm/s, 272 ms duration), stimuli
that were well tolerated by young children. A higher platform
velocity was chosen for backward than for forward
translations because of the different response threshold for
the two situations (Forssberg and Hirschfeld, 1994). The
forward and backward trials were presented in a random
order, with a variable inter-trial interval of about 810 s.
EMG and kinematic recordingsSurface EMGs were recorded from the sternocleido-
mastoideus [neck flexor (NF)], rectus abdominis (RA), rectus
femoris (RF), neck, thoracic and lumbar extensor muscles
(NE, TE and LE) and hamstrings (HAM) on the left side of
the body. TE and LE were analysed together (TE/LE), as
they were usually activated in concert.
Additionally, we were able to record kinematics
simultaneously with the EMGs in five of the PWM children,
eight of the preterm control children and five of the full-term
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730 M. Hadders-Algraet al.
children. The kinematic data were recorded by an ELITE
system in a two camera configuration for 3 s, starting 1 s
prior to perturbation. Reflective markers were put on the left
side of the body (i) on the caput mandibulae, (ii) 1 cm in
front of the angulus mandibulae, (iii) on the anterior superior
iliac spine, and (iv) on the trochanter major. Additionally,
three markers were put on the lateral side of the platform.Off-line data processing consisted of the calculation of spatial
angles for the head (by a vector between markers 21), the
pelvis (markers 43) and the body sway (markers 41) in
relation to the horizontal axis. The ELITE data frequently
were incomplete, because the two camera systems often lost
track of a marker due to arm movements or slight rotations
of the head.
Data acquisition and analysisEMG analysis. The signals from the platform and the EMGs
were sampled at 800 Hz, digitized at 12-bit resolution and
stored on SC/ZOOM, a dedicated signal analysis computer
system (Department of Physiology, Ume University,
Sweden). The software program converted the signals to
root mean square with a 6 ms moving window averaging
technique. A graphics terminal was used to define
interactively EMG events for each trial separately. The
interactive assessment offered the possibility to differentiate
EMG bursts from regularly occurring electrocardiac activity,
which especially was present in RA. EMG base-line activity
was defined as the mean activity recorded 500 ms prior to
each perturbation. A perturbation related EMG burst was
considered to be present when, during the time the platform
moved, a burst occurred lasting at least 30 ms and exceeding
base line activity by 2 SD. Likewise EMG inhibition was
defined as a drop of activity below 1.5 SD of the baseline
level, which lasted for at least 30 ms.
The first step in the analysis consisted of the documentation
of muscle activation patterns by describing the presence of
bursts and inhibition in the recorded muscles. This resulted
for each child in each condition (forward-slow, forward-fast,
backward-slow, backward-fast) in rates of EMG events per
muscle and rates of muscle activation patterns. The response
rates were calculated for each child and each condition by
dividing the number of trials with a response by the total
number of trials. Response rates were calculated for the
direction-specific agonist muscles and for the antagonistmuscles. The activity of the direction-specific agonist muscles
was also expressed in patterns of muscle activation, i.e. in
the combinations in which agonists were activated in concert
(see Fig. 4). This resulted in a response rate of specific
patterns and in a pattern variation index (number of different
patterns divided by the number of trials).
The next step consisted of the analysis of EMG amplitudes
and latencies. Latencies were defined as the time-interval
between the onset of platform movement and the onset of
an EMG response. In order to be able to compensate for the
age-dependent changes in body-size, absolute latencies were
also transformed into relative latencies by dividing latencies
(in milliseconds) by body length (in metres). Amplitudes
were computed by calculating the mean amplitude during a
period of 100 ms and 400 ms, respectively, starting at the
onset of the first burst belonging to the postural response.
The baseline activity was subtracted from these raw mean
amplitude values. The amplitude during the 100 ms periodreflects the power of muscle activation during the early phase
of the response, whereas the amplitude during the 400 ms
period represents the overall activity, including the activity
based on long latency processes of presumed transcortical
origin (Marsdenet al.,1983; Palmer and Ashby, 1992). Mean
latencies and amplitudes were calculated for each child in
each condition separately. The effect of platform velocity on
EMG amplitude was expressed by means of an EMG velocity
ratio consisting of the ratio between mean EMG activity
during fast translations and that during slow translations.
The effect of brain lesions was evaluated with help of the
matched pairs design allowing for the use of the Wilcoxon
test. For the analysis of within-group differences (e.g. type
of brain lesion in preterm children, type of neurological
condition at follow-up) and the differences between all
preterm and full-term children the MannWhitney test was
used.
Kinematic analysis. Focus was on the angular values at
movement onset and the angular displacements (the difference
between peak value and onset value) of head, pelvis and
body sway. Pearsons correlation coefficient was used for the
calculation of correlations between initial sitting position and
angular displacement on the one hand and muscle activity
on the other hand. Before entering the angular values at
movement onset and the EMG amplitudes into the
correlations, the data were normalized. The initial angles
were normalized by subtracting the childs mean initial angle
from the actual trials value. The EMG amplitudes were
normalized with respect to the maximal amplitude (100%)
produced by the child in the relevant muscle and time-window.
Throughout the study differences and correlations where
P 0.05 were considered to be statistically significant. For
brevitys sake only the data during the fast translations will
be reported, unless there is a special need for the data
during the slow trials (e.g. in the evaluation of a platform
velocity effect).
Results
Neurological outcomeOnly one of the preterm children with a PWM lesion had no
neurological dysfunctions at follow-up. Nine children of the
PWM group showed minor neurological dysfunction and
three had developed a cerebral palsy, each of them a different
form: a spastic diplegia, a spastic hemiplegia and a spastic
tetraplegia with mental retardation and epilepsy. The children
with the diplegia and hemiplegia were able to walk without
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Postural adjustments in preterm children 731
Fig. 1 Neurological outcome at pre-school age in preterm childrenwith and without PWM lesions and full-term children. Numberswithin brackets indicate the number of children in each group.US ultrasound findings; no data available; W3 periventricular cyst formation, without () and W3 with ()obvious loss of PWM; W4 large, intense echo densitiesextending into the deep layers of the white matter. CP cerebralpalsy; FT full-term; MND minor neurological dysfunction;N normal; PT preterm; MND hypotonia: mild diffusehypotonia and collapsed posture; MND block: see text; MNDawkward: movements (including speech movements) lack co-ordination and planning.
aids; the child with the tetraplegia was severely handicapped
and could not sit without help. The most frequent form of
minor neurological dysfunction was the so-called block
type of minor neurological dysfunction, which was
characterized by a stiff and block-like motility, an absence
of spontaneous rotations during standing and walking, and
mild problems in balance control. Muscle tone and tendon
reflexes were normal, but when testing the resistance against
passive movements, muscle tension rose rapidly when minor
increases in the velocity of the testing movements occurred.
In the preterm control group 12 children had a normal
neurological condition at pre-school age and one child showed
minor neurological dysfunction. All children born at term
were free from neurological dysfunction.
Neurological outcome was clearly related to the presence
and the severity of the brain lesions on the neonatal
ultrasounds (Fig. 1 and Table 2). Outcome was worse in case
of a W4 lesion or a W3 lesion with evident signs of tissue
loss in the PVM. No obvious relationship was present between
outcome and the presence and type of the asymmetry of
the lesions.
Direction-specific muscle activityForward and backward translations of the platform induced
a sway of the body in the opposite direction in all children.
All but one of the children were able to maintain balance
during the platform perturbations. They showed direction-
specific postural adjustments, consisting of a preference for
the activation of the ventral muscles during a backward sway
of the body and a primary activation of the dorsal postural
muscles during a sway of the body in the opposite direction
(Figs 2 and 3).
This basic level of postural control was absent in the child
with spastic tetraplegia, who was unable to sit without help
(Figs 2 and 3). He showed no responses during forward
translations. During backward translations he reacted with
an occasional weak activation of the direction specific dorsal
muscles, most frequently of the NE (36% of the trials),
which was followed by a late and clear response in the
ventral muscles.The activation rates of the individual direction-specific
agonist muscles during forward and backward translations
did not differ between the three groups. A difference was,
however, present in the rate of extensor inhibition during
forward translations. Such an extensor inhibition is in young
children part of the response pattern during forward
translations, but with increasing age extensor inhibition
gradually disappears (Fig. 2). Extensor inhibition occurred
in the present full-term children older than 212 years in 12%
of the trials (median value). When excluding the non-
responding tetraplegic child, the rate of extensor inhibition
was 90% in the group of children with PWM lesions over
212years, indicating a significant difference with the full-term
group (Wilcoxon, P 0.05). The rate of extensor inhibition
in the preterm control group fell in between that of the other
two groups (62%), thereby showing no statistically significant
difference with either.
Besides the response rates of the individual agonist
muscles, we also evaluated the way in which the agonists
were activated in concert. This resulted in a large variety of
response patterns (Fig. 4).
None of the patterns during forward or backward
translations occurred more often in a specific group of
children. This also held true for the patterns in which all
agonists participated (NF RA RF and NE TE/LE
HAM, respectively), patterns which are known to show
developmental changes (Hadders-Algra et al., 1998). Still a
remarkable difference was found between the PWM and
control groups in the response patterns during forward
translations. The difference was found in the variation of the
patterns within an individual child (Fig. 4). The response
variation during forward translations was significantly lower
in the PWM group than in both control groups, as was
reflected by a significant difference in the pattern variation
index (Fig. 5). The pattern variation index was related to the
presence of a PWM lesion, but not to its severity. Neither
did the pattern variation index show a relationship with the
neurological condition at follow-up. The pattern variationindex during backward translations did not differ between
the three groups.
Antagonist muscle activityDuring normal development antagonistic muscle activity is
transiently present between 9 months and 2123 years,
especially during forward translations (Hadders-Algra et al.,
1998). All full-term and the majority of preterm children
followed this developmental pattern of antagonist activity.
Two children were an exception to this general rule: the child
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732 M. Hadders-Algraet al.
Table 2 Ultrasound brain lesions and neurological outcome
Child Neonatal ultrasound scans of the brain* Follow-up
Haemorr. PWM Localization Asym. Tissue loss Age (years) Neurological condition
1 B3 W4 A M P R L 3.0 CP, spastic hemiplegia R
2 B3 W4 A M P R
L
3.5 CP, spastic diplegia3 B3 W4 A M P R L 3.5 MND, block-like motility
4 B3 W3 A M P R L 4.5 CP, spastic tetraplegia5 B3 W3 A M R L 2.0 MND, block-like motility6 B2 W3 A R L 3.0 MND, block-like motility7 B2 W3 A R L 4.5 Normal8 B0 W3 M R L 3.0 MND, block-like motility9 B0 W3 A R L 2.5 MND, awkward motility10 B0 W3 A M P R L 3.0 MND, mild hypotonia11 B0 W3 A M P R L 2.0 MND, block-like motility12 B0 W3 A M R L 4.5 MND, block-like motility13 B0 W3 M L R 1.5 MND, block-like motility
*Ultrasound classification according to Hesser et al., 1997 (see Methods). Haemorr. haemorrhages: germinal matrix (GMH) andintraventricular (IVH): B0 no haemorrhages, B2 GMH IVH without ventricular dilatation, B3 GMH IVH with ventriculardilatation; PWM periventricular white matter lesions; Localization: A anterior, M middle, P posterior; Asym. asymmetries:
L left, R right. borderline diplegia: no overtly handicapping condition, minimal hypertonia of legs, brisk tendon reflexes,Babinski R. CP cerebral palsy; MND minor neurological dysfunction.
with spastic diplegia (312 years) and the child with spastic
hemiplegia (3 years). These two children showed considerable
antagonist activity during forward translations, with NE, TE
and HAM showing a response in at least 50% of the trials
(in the hemiplegic child on both sides of the body). They
also showed unusual antagonist activity during backward
translations. In the diplegic child this antagonist activity was
restricted to the leg muscles (RF was activated in 30% of
the trials), whereas in the hemiplegic boy, the antagonist
activity occurred bilaterally from leg to neck (RF 100%, RA
5062%, NF 1244%). The pattern of antagonistic activity
was variable in all groups, with a pattern of co-activation
prevailing in the neck and leg muscles, and a pattern of
reciprocal activity dominating the trunk muscles.
Timing of agonist activityUp until 412 years of age, the relative latencies to agonist
activation during forward and backward translations decrease
significantly with increasing age. The latencies are not
affected by the velocity of the perturbation (Hadders-Algra
et al., 1998) (Fig. 6). All children of the full-term and preterm
control groups had age-adequate response latencies, whilethe relative latencies of the children in the PWM group, who
were older than 2 years, were considerably shorter than those
of the full-term group [during forward translations: NF, P
0.04; RA, P 0.09 (ns); RF, P 0.01; during backward
translations: NE, P 0.01; TE, P 0.07 (ns); HAM, P
0.14 (ns); Fig. 6]. The relative latencies were not related to
either the severity of the PWM-lesion or the neurological
condition at follow-up. The finding of reduced latencies in
children with significant brain lesions was supported by the
presence of a significant asymmetry in the latencies in the
child with spastic hemiplegia. The latencies on the affected
side of his body were significantly shorter than those on the
unaffected side [paired t test, differences during forward
translations: NF, P 0.01; RA, P 0.19 (ns); RF, P
0.01; during backward translations: NE, P 0.05; TE, P
0.38 (ns); HAM, P 0.01].
The sequence in which the agonistic muscles were recruited
during forward and backward translations showed
considerable variation in all groups. The order of muscle
recruitment was not clearly related to the presence or the
severity of a PWM lesion, preterm birth or the neurological
condition at follow-up.
Modulation of agonist EMG amplitudeFrom 9 months onwards children can modulate the EMG
amplitude of the agonistic ventral muscles during forward
translations with respect to platform velocity: a higher
platform velocity results in a moderate, but significant
increase of the EMG amplitudes (Hadders-Algraet al., 1996a,
1998). All children in the present study (except for the
child with the tetraplegia) showed this modulating capacity.
Remarkably, from the age of 212 years onwards, the velocity
effect turned out to be stronger in the preterm children thanin the full-term children. This difference in sensitivity to
platform velocity was reflected by significantly higher
velocity ratios of RA100and RF100(the mean amplitudes over
the first 100 ms of the response) in the preterm than in the
full-term children (Fig. 7). The higher velocity ratios were
found in both groups of preterm children, indicating that this
effect was not related to the presence of PWM lesions, but
to the preterm birth itself. Within the preterm children the
velocity ratios were not related to gestational age at birth,
birthweight or neurological condition.
In none of the children without cerebral palsy, nor in the
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Postural adjustments in preterm children 733
Fig. 2 Response patterns during forward translations. Average activity during eight fast translations. Note the absence of extensorinhibition in the full-term (FT) child of 4 years, the brisk agonist activity and extensor inhibition in the preterm (PT) children (all fromthe PWM group), the antagonist activity in the diplegic and hemiplegic child and the absence of response activity in the tetraplegic child(single trial). MNDA minor neurological dysfunctionawkward; MNDB minor neurological dysfunctionblock; PLF platformdisplacement; NF neck flexors; NE neck extensors; RA musculus rectus abdominis; TE thoracic extensors; LE lumbarextensors; RF musculus rectus femoris; HAM hamstring muscles. Time calibration (horizontal bar): 100 ms; amplitude calibration(vertical bar): 0.4 mV.
child with spastic tetraplegia, was a velocity effect on EMG
amplitude present during backward translations, but the
children with spastic diplegia and spastic hemiplegia did
have such a velocity effect in the dorsal muscles. The boywith spastic diplegia showed significant velocity effects in
NE100 and TE400 (paired t test: P 0.02 and P 0.0001,
respectively) and the boy with hemiplegia demonstrated a
velocity effect bilaterally in TE400and HAM100(pairedttest:
P 0.01 and P 0.02, respectively) and on the unaffected
side in NE100(paired t test: P 0.001).
From 9 months onwards children are also able to modulate
EMG amplitude during forward translations with respect to
sitting position. The modulating effect is brought about by
initial pelvis position. Until about 3 years of age initial pelvis
position affects the amplitude of RF; in older children the
effect moves to NF (Hadders-Algra et al., 1996a, 1998). In
both groups of preterm children this modulating capacity
was totally absent (Fig. 8).
None of the full-term and preterm children showed duringthe present perturbation procedure, which consisted of two
series (a slow series and a fast series) of randomly distributed
forward and backward translations of a similar amplitude,
signs of central set or adaptation due to prior experience
(cf. Horaket al., 1989).
DiscussionThe present study revealed that the neural control of postural
adjustments in preterm children differs from that of age-
matched children born at term. Some of the postural
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734 M. Hadders-Algraet al.
Fig. 3 Response patterns during backward translations of the same children as represented in Fig. 2. Average activity during eight fasttranslations. Note the weak responses in the full-term (FT) child of 4 years, the moderate agonist activity in the minor neurologicaldysfunction children and the brisk agonist activity in the diplegic and hemiplegic child. The last recording is a single trial of thetetraplegic child (due to the variable and low agonist activation, the average recording did not show any response). In the present trial aresponse is present in NE and HAM, and after a longer interval there is significant activity in NR, RA and RF. For the abbreviations, seelegend of Fig. 2. Time calibration (horizontal bar): 100 ms; amplitude calibration (vertical bar): 0.4 mV.
dysfunctions were related to neonatal PWM lesions, others
to preterm birth itself. The presence of a PWM lesion was
not only associated with the development of neurological
dysfunctions, but also to deficient spatial and temporal
characteristics of the postural responses. Preterm birthaffected the ability to modulate the EMG responses. During
forward translations preterm children showed a higher
sensitivity to platform velocity than full-term children, but
they lacked the capacity to modulate EMG amplitude with
respect to initial sitting position.
Postural dysfunctions related to PWM lesionsSerious PWM lesions can result in a severely handicapping
condition, in which the subject cannot sit without help. One
of the children of the present PWM group developed such a
condition. His postural adjustments showed a profound
deficit: he did not show distinct direction-specific responses,
indicating that he lacked control at the basic level of postural
organization (cf. Forssberg and Hirschfeld, 1994). The
absence of direction-specificity cannot be attributed to theinability to sit without help, as non-sitting infants of 56
months do exhibit significant direction-specificity (Hirschfeld
and Forssberg, 1994; Hadders-Algra et al., 1996a). However,
the reverse is probably true: it is unlikely that children who
lack direction-specific postural responses develop the ability
to sit independently. Two explanations can be offered for the
absence of direction-specific responses: (i) the circuitries
producing the basic muscle patterns, i.e. the synergies, have
not developed, and (ii) the sensory pathways were not
sufficiently integrated to elicit activity in the synergies.
Variation is a primary property of normal neurological
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Postural adjustments in preterm children 735
Fig. 4 Distribution of response patterns during fast forward translations in the full-term (FT) and the preterm (PT) PWM group. Eachhorizontal bar represents the distribution of response patterns for one subject. The PWM group is ranked according to the severity of theneurological condition at follow-up; the age-matched FT control subjects are displayed on the same horizontal level as the PWMsubjects. N neurologically normal; MND minor neurological dysfunction; MND-H MND with mild hypotonia; MND-B MND-block; MND-A MND with awkward motility; CP-HE cerebral palsy with spastic hemiplegia, A denoting the affected sideand U the unaffected side; CP-DI spastic diplegia; CP-TE spastic tetraplegia. The explanation of the colour-codes is given in B. Inthis panel hatching of a square indicates participation of a muscle in a particular pattern. The unusual diagram should be read as follows.Take for instance, the first (upper row) child of the PWM group, who was exposed to eight fast translations. She responded during onetrial with NF RA, (12.5% black hatching), during three trials with the combination of NF RA RF (37.5% dark green shading)and during four trials she responded with the combination of extensor inhibition and NF RA RF activation (50% red shading).
development, including the development of postural control
(Touwen, 1978; Forssberg, 1985; Edelman, 1989; Hadders-
Algra et al., 1998). A rich variation at an early age allows
the selection of the most appropriate response pattern, which,
as a result of following developmental processes, can be
adapted to task specific constraints (Hadders-Algra et al.,
1996a). Possibly, substantial variation in postural responses,offering the possibility of selection of the best response, is
a prerequisite for the development of the ability to modulate
postural activity. This suggestion is supported by the present
study: the children with a PWM lesion showed a reduced
variation in postural responses, and an inability to modulate
their postural adjustments with respect to the initial sitting
position. Others also noted that a lack of variation, reflected
by the presence of monotonous and stereotyped motor
behaviour, is an early marker of an abnormal neurological
development (Touwen, 1978; Hadders-Algra et al., 1997).
Moreover, a similar lack of variation has been reported
for postural adjustments of children with spastic diplegia
(Brogren et al., 1998).
Animal research demonstrated that early brain lesions
induce complex types of reorganization, the type depending
on the site and the size of the lesion and the subjects age at
the insult (Kolb and Whishaw, 1989). Undamaged parts of
the brain can take over functions of the lesioned parts, butthis may be at the expense of the quality of other functions
served by the hosting tissues (Huttenlocher and Raichelson,
1989; Kolb and Whishaw, 1989). The limited data available
on neural reorganization after early brain damage in humans
confirm the presence of complex patterns of reorganization,
such as the possibility of functional compensation by
undamaged parts of the brain (Brouwer and Ashby, 1991;
Carr et al., 1993). Our data corroborate the idea of complex
reorganization: in all but one of the children with a PWM
lesion the basic level of postural control had developed,
albeit with the help of seemingly simplified neural circuitries
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736 M. Hadders-Algraet al.
Fig. 5 Response pattern variation index during fast forwardtranslations in the three groups. The data are presented by ranges(vertical bars), interquartile ranges (shaded boxes) and medianvalues (horizontal bars). The asterisks indicate statistically
significant differences in pattern variation index between thegroups (Wilcoxon): *P 0.05, **P 0.01. FT full term,PT preterm, US-N normal ultrasound scans of the brain,PWM lesion of the periventricular white matter.
containing fewer interneuronal connections. Such simplified
circuitries would generate little variation in the output
patterns, and require relatively little processing time. This is
exactly what we found in the children with a PWM lesion:
less variation in the postural responses and shorter latencies
until response onset.
The shorter latencies (with a reduction in absolute values
of ~10 ms) seem to be at variance with the common finding
of longer latencies to various responses in children with brain
dysfunction. Two factors might explain the discrepancy. First,
differences in the type of the evaluated responses might play
role, e.g. visual or somatosensory evoked potentials or
cutaneomuscular reflexes (Evans et al., 1991; Cooke, 1992;
Taylor, 1992) versus postural adjustments in the present
study. Secondly, the age of the subject appears to be an
important factor. The majority of studies reporting longer
latencies to responses in children with brain dysfunction (e.g .
latencies to somatosensory or visual evoked potentials) have
been performed during the first year of life (Cooke, 1992;
Taylor, 1992). Also in the present study the younger children
tended to have increased latency values, whereas only afterthe age of 2 years were the shorter latencies found (Fig. 6).
This might imply that certain developmental processes in the
nervous system should have occurred (see Hadders-Algra
et al., 1998) before short-for-age latencies to motor responses
in children with brain-damage can be found. This, in turn,
could explain why others, who looked for longer latencies
in sensorimotor responses of children with brain dysfunction,
failed to find unequivocally longer latency values (Evans
et al., 1991; Mu
ller et al., 1992). The short-for-age latencies
could be due to altered polysynaptic spinal pathways induced
by the early damage of the brain (cf. Berger et al., 1985;
Harrison, 1988; Hadders-Algra, 1993; Myklebust and
Gottlieb, 1997).
The children of the PWM group showed more extensor
inhibition during forward translations than the control
children, slightly more than the preterm controls and
significantly more than the full-term controls. A prerequisite
for the manifestation of extensor inhibition in the EMGrecordings is a relatively high tonic background activity in
the dorsal extensor muscles (Hadders-Algra et al., 1996a).
This indicates that the preterm children, and especially those
with a PWM lesion, had a significantly higher tonic activity
in their neck and back muscles. It is conceivable that this
relatively high tonic activity in the extensor muscles is an
expression of the same pathophysiological condition which,
at earlier ages, produces the posture of hyperextension of
neck and trunk so characteristic of many preterm infants
(Drillien, 1972; Touwen and Hadders-Algra, 1983; De Groot
et al., 1992).
The majority of children with a PWM lesion did not differ
from the control children in the amount of antagonistic co-
activation. An excessive amount of antagonistic co-activation
was only found in the two children with a moderate form of
cerebral palsy, which is in agreement with findings of others
on postural control in children with spastic cerebral palsy
(e.g. Berger et al., 1984, 1985; Brogren et al., 1996, 1998;
Woollacott et al., 1998). The excessive co-activation can be
regarded as a primary dysfunction, based on altered intra-
and supra-spinal circuitries due to the early brain lesion
(Leonardet al., 1991a; Myklebust and Gottlieb, 1997), or as
a secondary phenomenon, as it could serve also as a functional
compensation for the postural instability inherent to cerebral
palsy (Woollacottet al., 1998). The finding of equal amounts
of co-activation on both sides of the body in the boy with
spastic hemiplegia might be an argument in favour of the
latter explanation.
The present study revealed that PWM lesions are related
to significant postural dysfunctions in the age period of 1 12
412 years. Whether or not the dysfunctions remain present at
older age needs to be determined. For the children with
cerebral palsy, it seems likely that the postural problems
persist, as EMG studies on the development of locomotor
behaviour in these children with cerebral palsy indicated that
the basic motor deficits do not change with increasing age
(Berger et al., 1984; Leonard et al., 1991b). Whether the
same holds true for the children with minor neurologicaldysfunction is less clear, as the expression of minor
neurological dysfunction changes substantially between
toddler age and adolescence (Hadders-Algra and Touwen,
1999).
Postural dysfunctions related to preterm birthPreterm birth was associated with an altered capacity to
modulate EMG amplitude during forward translations. First,
preterm children showed a higher sensitivity to platform
velocity than children born at term. This could point to a
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Postural adjustments in preterm children 737
Fig. 6 Relative response latencies during fast forward and backward translations in the PWM group. The hatched areas denote the rangeof relative latency values found in a previous study on postural adjustments in healthy full-term pre-school age children (Hadders-Algraet al., 1998); the horizontal bars indicate the median values of this full-term-reference group. The asterisk indicate statistically significant
differences between the age-groups of the full-term children (KruskalWallis): *P 0.05, **P 0.01,***P 0.001. The black dotsrepresent the relative latency values of the individual children of the PWM group (n 1012, due to the interindividual variation inmuscle activation).
higher velocity sensitivity of muscles to stretch, analogous
to that of spastic children, which has been attributed to
changes in the intraspinal circuitry, such as low degree
of presynaptic inhibition of the muscle spindle afferents
(Crenna, 1998).
Secondly, preterm children lacked the ability to modulate
EMG amplitude with respect to initial sitting position.
Normally, this ability develops at 910 months (Hadders-
Algra et al., 1996a), indicating that from this age onwards,infants have access to complex postural control mechanisms
consisting of three basic components: (i) afferent information
on the orientation of body segments, including the information
from load receptors (cf. Bergeret al., 1995), and the position
of the centre of gravity; (ii) an internal postural reference
frame; and (iii) postural motor output (Massion, 1994).
Training experiments demonstrated that daily balance practice
accelerates the development of the modulating ability by 2
months (Hadders-Algra et al., 1996b), suggesting a role of
experience and learning. The inability of preterm children to
modulate the postural adjustments with respect to the sitting
position can be the result of dysfunction in any of the three
basic components. Considering the fact that preterm children
are at substantial risk for the development of learning
disorders (Hille et al., 1994), it can be hypothesized that
their inability to modulate postural responses to initial sitting
position is the result of a deficient capacity to learn from
prior experience. More specifically, this might point to a
dysfunction in the cerebellum or the basal ganglia, as these
systems play a particular role in the fine-tuning of motoroutput, including postural adjustments, to the environment
on the basis of prior experience (Bloedel, 1992; Graybiel,
1995; Kimura, 1995). The better candidate of these two
systems seems to be the basal ganglia, as a recent grip-and-
lift study of children with unilateral brain damage revealed
that, besides extensive cortical lesions, lesions of the basal
ganglia were associated with disturbances in the long-lasting
developmental process of the grip-lift synergy (Forssberg
et al., 1999). This is in line with Graybiels suggestion (1995)
that the basal ganglia might play a specific role in the
development of new motor patterns, i.e. in the formation of
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738 M. Hadders-Algraet al.
Fig. 7 Velocity ratios (VR) in ventral muscles during forwardtranslations in children 2 years. Velocity ratios (ratio of meanamplitude during fast perturbations and mean amplitude duringslow perturbations) of NF100, RA100and RF100 in children born atterm (n 10; open bars) and preterm children with and withoutPWM lesions (n 19; black bars). NF100, RA100 and RF100denote the mean amplitudes during the first 100 ms of thepostural response in the neck flexor (NF), musculus rectusabdominis (RA) and musculus rectus femoris (RF), respectively.The data are presented by ranges (vertical bars) and medianvalues (horizontal bars). The asterisks indicate statisticallysignificant differences between the full-term and preterm children(MannWhitney): *P 0.05, **P 0.01.
procedural memories. In this respect it is also interesting to
note that results from animal research indicated that the basal
ganglia seem to be particularly vulnerable to perinatal stress,
as early mild chronic hypoxia can result in long-term changes
in the striatal dopaminergic system (Gross et al., 1993).
Possibly, preterm birth, which is associated with a variety of
perinatal stresses, such as minor hypoxic insults, can induce
adverse changes in the basal ganglia which cannot be detected
on the neonatal ultrasound scans of the brain.
Concluding remarksThe present study revealed that preterm birth is associated
with two types of postural dysfunction. One is related to
distinct PWM lesions and consists of a limited repertoire of
response variation. The other dysfunction is not related to
lesions, which can be detected on neonatal ultrasounds of
the brain. It consists of a shift of postural control which is
guided by feedforward processes based on prior experience,to a form of postural control which is dominated by feedback
mechanisms.
AcknowledgementsWe thank Ingmarie Apel, Elien Oldekamp, Anneke Klip-Van
den Nieuwendijk and Roelof Hadders for technical assistance.
The study was supported by the Swedish Medical Research
Council (4X-5925), Norrbacka-Eugenia Stiftelsen, Sunner-
dahl Handikapp Fond, Josef och Linnea Carlssons Stiftelse,
Fo
rsta Majblommans Riksfo
rbund and Sven Jerring
Fig. 8 Correlations between (normalized) initial pelvis angle and(normalized) EMG amplitude in the RF muscle (RF100) duringslow forward translations in children 4.5 years. Available data:full-term (FT) group: 26 trials of four children; preterm (PT)control (US-N normal ultrasound): 24 trials of five children;PT-PWM without cerebral palsy: nine trials of two children.n.s. not significant.
Stiftelsen. M.H.A was supported by a grant from the Ter
Meulen Fund, Royal Netherlands Academy of Arts and
Sciences.
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Postural adjustments in preterm children 739
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Received August 28, 1998. Revised November 12, 1998.
Accepted November 18, 1998