Clinical assessment of motor behaviour in developing children
Kuiper, Marieke Johanna
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Kuiper, M. J. (2018). Clinical assessment of motor behaviour in developing children. Rijksuniversiteit Groningen.
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MJ Kuiper
CHAPTER 1
This thesis is about the clinical assessment of motor behaviour in developing children, both under physiological and pathological conditions. During normal, physiological development, the motor behaviour of children shows immature co-ordination and motor control, potentially resembling features of movement dis-orders. This resemblance between physiological motor behaviour and features of movement disorders may complicate the early recognition and clinical assessment of movement disorders. For example, when treatment options are evaluated with rating scales, longitudinal improvements by maturation could run the risk of being over-interpreted as treatment effects. Thus, insight in the physiological values of movement disorder rating scales would contribute to reliable assessment of move-ment disorders under pathological conditions. In this perspective, we aimed to elucidate the influence of physiological motor development on movement disorder assessment tools (i.e. phenotyping and rating scales) in the first part of this thesis (chapter 2-6). In the second part, we aimed to use the physiological values of the first part for adequate clinical assessment of movement disorders after perinatal asphyxia (chapter 7) and lead intoxication (chapter 8).
NORMAL PHYSIOLOGICAL MOTOR DEVELOPMENT
Motor behaviour is a commonly used term that includes every kind of move-ment, from involuntary patterns in infants to goal-directed voluntary movements in adults.1 The development of motor behaviour starts early in gestation, shows
major changes during childhood and is associated with the maturation of the central nervous system (CNS).2 Development of the CNS starts with the
forma-tion and closure of the neural tube at 28 days of gestaforma-tion. Between the second and fifth month of gestation, neurons and glia cells proliferate and migrate to subcortical structures and the cerebral cortex.2 From this period onwards (i.e. >8
weeks of gestation), the developing CNS produces movement patterns that occur involuntarily, such as isolated limb movements, yawning, breathing, startles, the asymmetrical tonic neck reflex (ATNR) and general movements (GMs; a series of gross movements of variable speed and amplitude that involve the whole body).3-5
GMs are generated by spontaneous activity of central pattern generators (CPGs) in the spinal cord and brain stem.5-8
The subsequent period, from the fifth month of gestation to two years post term, is called the organization period. During this period, neural networks are formed between the spinal cord, brainstem, thalamus, basal ganglia, cerebral cortex and cerebellum.2 During the first year of life, the activity of these networks
gradu-ally increases, leading to the inhibition of involuntary movement patterns. In the same period, directed, voluntary motor patterns are initiated. The first
goal-directed movement patterns, such as voluntary grasping, can be observed from the age of three months onwards. Other voluntary movements, such as rolling, sitting and walking develop subsequently and are usually acquired before the second year of age.9,10 After development of these simple movements, more complex
move-ments, such as alternating and sequential hand and foot movemove-ments, are acquired before the fifth year of age, see figure 1.11,12 During childhood, the quality of both
simple and complex goal-directed, voluntary movements will gradually change from a clumsy appearance into fluent, precise and well-coordinated motor per-formances.10,12,13
The development of motor behaviour is attributed to the fine-tuning by activity-dependent synaptic elimination and myelination of neural networks between the cerebellum, basal ganglia, thalamus, and cerebral cortex.2,14 Each network has a
specific contribution to the motor performance. The basal ganglia networks are especially important for the motor control by facilitating desired motor patterns and inhibiting competing motor patterns.15,16 Cerebellar networks are especially
important for the planning and execution of refined, coordinated movements and postural control.17 The maturation of the basal ganglia and cerebellum can be
in-directly measured by the volume of white (i.e. myelination) and grey matter (i.e. neurons, glia cells and synapses) on MRI, see figure 1.18 Under pathological
condi-tions, this process of CNS maturation and motor development can be disrupted, potentially leading to movement disorders.
MOVEMENT DISORDERS IN CHILDHOOD
Movement disorders can be defined as an excess of movements (i.e. hyperkinetic), a paucity of voluntary movements (i.e. hypokinetic) or an inability to generate a normal voluntary movement trajectory (i.e. ataxia).15,19 Commonly observed
pae-diatric movement disorders involve dystonia, chorea, myoclonus, tremor, tics and ataxia.15 The aetiology of such paediatric movement disorders is heterogeneous,
including genetic, metabolic, hypoxic-ischemic, toxic and inflammatory causes.15,20
The type of movement disorder depends on the dysfunctional connections within the motor network.20 In this thesis, we will focus on dystonia and ataxia, which are
associated with dysfunctional basal ganglia and cerebellar networks.15,20 Dystonia
is by definition characterized by involuntary sustained or intermittent muscle contractions causing abnormal, often repetitive, movements and/or postures.21
Ataxia is characterized by the impaired smooth performance of goal-directed movements, resulting in impaired ‘unconscious’ decision making about balance, speed, force and direction of intended movements.17,22,23
In clinical practice, recognition and adequate description of these movement disor-ders (i.e. phenotyping) is crucial. Phenotypic assessment involves the classification of movement disorders according to the definitions described above for dystonia and ataxia.21 The severity of the movement disorder is subsequently assessable
by quantitative rating scales.24,25 Accurate application of both phenotypic (i.e.
qualitative) and quantitative movement disorder assessment tools are essential for (1) unambiguous communication between clinicians, (2) adequate treatment evaluation, (3) unanimous categorization and data entry in international databases and (4) homogeneous patient inclusion in clinical research trials.26
Figure 1. Time line of physiological motor development and brain maturation
Green boxes indicate the physiological motor development, including early neonatal movement patterns, primitive reflexes and voluntary motor milestones. Orange boxes indicate the maturational processes in the central nervous system. The boxes with the brain regions (cerebral cortex, basal ganglia and cerebellum) indicate the maturation determined by a peak in grey matter on MRI. The motor development reflects the CNS maturation. ATNR = Asymmetrical Tonic Neck Reflex; GMs = General Movements
INFLUENCE OF PHYSIOLOGICAL MOTOR DEVELOPMENT ON MOVEMENT DISORDER ASSESSMENT TOOLS
Most clinical assessment tools for movement disorders are originally developed for adults, although the same assessment tools are identically applied in chil-dren as well. In young chilchil-dren, immature motor behaviour may physiologically reveal suboptimal coordination, co-contractions and overflow movements during complex motor tasks, which may resemble movement disorders (i.e. movement disorder-like features). For instance, the toddlers gait may resemble an ataxic gait and physiological overflow movements may resemble dystonic posturing. It is thus important to realize that immature motor behaviour in developing children could influence movement disorder assessment tools.9,10,12,13 When the child grows
up, these immature movements develop into fluent, precise and well-coordinat-ed movements and the movement disorder-like features tend to disappear. This implicates that movement disorder assessment tools should be interpreted in an age-related way. In the first part of the thesis, we therefore aimed to elucidate the influence of age on qualitative (i.e. phenotypic features; chapter 2) and quantita-tive (i.e. rating scale scores; chapter 3, 4 and 6) movement disorder assessment tools, in healthy typically developing children. Furthermore, ataxia rating scales also include speech sub-scores as part of coordinated motor output. It is there-fore important to consider the influence of age on speech sub-scores as well. For official speech sub-scores, the child has to speak some sentences in their native language. In international databases, these speech recordings can be assessed by observers with a different native language. This could not only lead to increased inter-observer variation (in comparison with motor tasks), but also to bias due to different complexity of each language.27 For reliable data entry in international
databases, we investigated whether we could avoid a language bias by replacing official speech subscores by universal syllable repetition tasks (SRT; chapter 5). Insight in the age-related influence on movement disorder assessment tools is important for several reasons. First, it may increase our knowledge about the maturation of underlying motor centres and networks. Second, it may contribute to early recognition of the first mild features of initiating movement disorders by comparing the motor behaviour with healthy children. Third, it may contribute to reliable interpretation of movement disorder severity and the evaluation of treat-ment options. For instance, physiological motor developtreat-ment of healthy children will have an effect on longitudinal rating scale scores. When such longitudinal “improvement” by maturation is observed under pathological conditions, one could falsely interpret this as small treatment effects. This is particularly essen-tial since treatment options are nowadays already considered in children younger
than 4 years of age (who will reveal clear “improvement” of coordination and accuracy by age).28-30
Altogether, forthcoming insight in the age-related influence on movement disorder assessment tools may allow reliable implementation of these assessment tools under pathological conditions.
CLINICAL ASSESSMENT OF MOTOR BEHAVIOUR UNDER PATHOLOGICAL CONDITIONS
In the second part of this thesis, we implemented the physiological age-related outcomes in the interpretation of pathological conditions. The first patient group consists of children who suffered from hypoxic-ischemic encephalopathy (HIE) due to perinatal asphyxia at a term age. Perinatal asphyxia around term age may result in damage of the deep nuclear structures (basal ganglia and thalamus), cerebral cortex and corticospinal tracts.2,31 Injury in these regions is associated
with dystonia, choreoathetosis, spasticity and/or hypotonia (as part of (dyskinetic) cerebral palsy).31,32 The prevalence and severity of these neurological symptoms
has significantly improved with the introduction of therapeutic hypothermia.33,34
In chapter 7, we described the neurological outcome (including qualitative and quantitative assessment of movement disorders) in post-asphyxiated children treated by therapeutic hypothermia and compared outcomes with healthy age-related controls.
OUTLINE OF THE THESIS
The aim of this thesis is twofold. In the first part of the thesis, we aim to eluci-date the influence of age on movement disorder assessment tools in typically developing children (chapter 2-6). In chapter 2, we investigated the neurological phenotype of developmental motor patterns in healthy infants and toddlers (0-3 years of age). In chapter 3 and 4, we studied the influence of age on frequently applied dystonia and ataxia rating scales in healthy school aged children (4 – 16 years of age). In chapter 5, we investigated whether speech sub-scores of ataxia rating scales can be reliably assessed for application in international databases. We additionally studied whether replacement of official speech subscores by syllable repetition tasks could provide reliable outcomes. In chapter 6, we compared the physiological age-related effect between dyskinesia, dystonia and ataxia rating scales in healthy children (4-16 years of age).
In the second part of this thesis (chapter 7-8), we aimed to implement the move-ment disorder assessmove-ment tools in children under potentially pathological
condi-tions. In chapter 7, we evaluated the neurological outcome in children who were treated with hypothermia after perinatal asphyxia, who are at risk for developing dystonia as part of dyskinetic cerebral palsy. In chapter 8, we assessed the neu-rological outcome in a cohort of Peruvian, lead intoxicated children, who are at risk of developing ataxia.
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