Original articleAbnormal general movements in girls with Rett disorder: The first four months of life
Introduction
In the observation of young infants the focus of interest has changed from the analysis of the infant's capacity to respond to a range of sensory stimulations to the observation of the un-stimulated infant. Naturalistic observation led to the conclusion of the dominance of spontaneous behaviour—i.e. behaviours endogenously generated by the young nervous system and not generated by sensory stimulation (for a review see [1]). Spontaneous movements have a long prenatal history; they occur in distinct motor patterns from 8 weeks postmenstrual age onwards [2], [3], [4]. The first movement to occur is sideward bending of the head. At 9–10 weeks postmenstrual age, complex and generalized movements occur. These are the so-called general movements (GMs) [5] and startles. Both include the whole body, but the general movements are slower and have a complex sequence of involved body parts, while the startle is a quick, phasic movement of all limbs, trunk and neck [4]. The majority of foetal movement patterns develop during the first half of pregnancy and continue not only until term but also after birth. Amazingly, there are hardly any changes in the form and pattern of the spontaneous movements immediately after birth, despite the profound changes in the environmental condition. During the first 2 months postterm the human neonate demonstrates a continuum of neural functions from prenatal to postnatal life. GMs occur with a writhing character with large amplitude ellipsoid components, particularly in the arms. Around the third month a major neurological transformation occurs [6], [7]. The infant's head is no longer positioned to the side but is now held centred in the midline; muscle power is rapidly increasing and can more easily overcome the force of gravity, including proper head control; GMs gradually lose the writhing character and a new pattern of GMs, the fidgety movements, emerges [8]. The neural mechanisms of GMs involve central pattern generators in the brainstem. Separate generators are assumed to be responsible for both GMs of writhing and of fidgety character, as both patterns may be seen simultaneously during a period of overlap [9], [10].
After the change in paradigm from reflex to spontaneous motor activity was achieved, the way was paved for the discovery of the importance of the quality of GMs in assessment of the integrity of the young nervous system [1], [11]. Infants with brain damage move differently from those with intact brains [1], [10], [11], [12], [13], [14], [15]. From studies on foetuses and infants with brain malformation [16], [17] it became clear that malformations of the forebrain and the diencephalon dramatically alter the expression of GMs to a chaotic movement pattern. Thus, an intact brain is a prerequisite for the normal quality of GMs. Consequently, the question was posed whether genetic brain disorders might have an impact on GM quality.
An apparently normal prenatal and perinatal period followed by an apparently normal psychomotor development during the first 6 months of life, were considered as criteria for classical Rett syndrome [18], [19]. However, careful retrospective analyses suggested that subtle behavioural disturbances might be present shortly after birth [20], [21], [22], [23]. Lack of response to the environment, autistic features and hypotonia were found in medical reports of the first months of life [21], [24], [25]. Retrospective parental inquiries revealed that the babies had been particularly placid, had an empty gaze, had slept too well, and had to be woken for feeds [21], [24], [25], [26], [27]. Based on family film analyses, some investigators had, however, failed to identify abnormal signs between birth and 12–18 months [28], [29]. By contrast, other video analyses clearly demonstrated that already the young infant with Rett disorder had abnormal repetitive limb and trunk movements [20], [25], [26].
In order systematically to study the early motor repertoire of infants with Rett disorder, we first carried out a pilot study on 17 daily life video clips taken by parents. We observed six normal infants and eight infants who later turned out to have Rett disorder during their first 6 months of life, and we were able correctly to identify all cases. This encouraging result led to a detailed video analysis of 22 girls with Rett disorder, which clearly demonstrated that all infants had abnormal signs during their first months of life. In addition to abnormal GMs, postural stiffness, and tremor, the first stereotypies of hand and body movements were described. The analysis of the face revealed asymmetrical eye opening and closing, bursts of abnormal facial expressions, tongue protrusion, and bizarre smile [30]. The most striking result was that none of the infants with Rett disorder had a history of normal GMs. We, therefore, felt the need to report on the GM assessment of these infants in more details. Specific questions we asked were:
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Do infants with Rett disorder have a specific pattern of abnormal GMs?
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What are their individual developmental GM trajectories?
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What are the characteristics of other age-specific motor patterns?
Section snippets
Patients and method
Videos of 26 girls with classical Rett syndrome, born between 1964 and 1997, were donated by British families (informed consent and ethics committee approval) for the purpose of a detailed behavioural analysis. Fourteen girls were recorded during their first 4 months of life and were thus available for the assessment of GMs. The recordings were performed by the families as part of their family archive without the knowledge that the child had Rett disorder. All but one was born at term. Case 20
Results
The quality of writhing movements could be reliably assessed in nine cases. All but two infants had abnormal writhing GMs (Table 1). The abnormalities consisted of a poor repertoire of GMs, in that the sequence of the successive movement components was monotonous and movements of the different body parts did not occur in the complex way seen in normal GMs [13], [31]. Four infants had predominantly jerky and fast movements (Cases 1, 7, 16, and 17, Table 1); two others moved in abnormally slow
Discussion
The quality of performance was the crucial part of our video analysis. Already the first reports on viewing some of these videos revealed jerky uncoordinated movements [20]. Our present detailed analysis demonstrated that the main pattern of spontaneous movements, the GMs, were clearly impaired in infants with Rett disorder [30].
During the first 2 weeks postterm age six infants were recorded; two of them had normal GMs (Table 1). These infants (Cases 3 and 5) were not recorded again within the
Acknowledgements
The study has partly been supported by the General Movement Trust. Dr Kerr's work has been supported by the Scottish, UK and International Rett Associations. We extend our sincere gratitude to the families who provided us with the videotapes we analysed for this paper. Their goodwill and cooperation made this work possible.
References (40)
- et al.
The emergence of fetal behaviour. I. Qualitative aspects
Early Hum Dev
(1982) New perspectives in early human development
Eur J Obstet Gynecol Reprod Biol
(1986)State of the art of a new functional assessment of the young nervous system. An early predictor of cerebral palsy
Early Hum Dev
(1997)Qualitative changes of spontaneous movements in fetus and preterm infant are a marker of neurological dysfunction
Early Hum Dev
(1990)- et al.
An early marker for neurological deficits after perinatal brain lesions
Lancet
(1997) - et al.
Posture, behavioural state organization and spontaneous movements in infants affected by brain malformation
Early Hum Dev
(1997) - et al.
The spectrum of phenotypes in females with Rett syndrome
Brain Dev
(2003) - et al.
Clinical features of the early stage of the Rett syndrome
Brain Dev
(1990) Rett syndrome: a retrospective pilot study on potential early predictive symptomatology
Brain Dev
(1987)- et al.
The hands, and the mind, pre- and post-regression, in Rett syndrome
Brain Dev
(1987)
The qualitative assessment of general movements in preterm, term and young infants—review of the methodology
Early Hum Dev
Pathophysiologies of Rett syndrome
Brain Dev
General movement assessment as a method of developmental neurology: new paradigms and their consequences. The 1999 Ronnie MacKeith lecture
Dev Med Child Neurol
Prenatal and early postnatal development of human motor behaviour
Fetal behaviour
Postures, motility and respiration of low-risk preterm infants
Dev Med Child Neurol
A qualitative approach to the development of movements during early infancy
Observation of movements during sleep in ALTE and apnoeic infants
Early Hum Dev
Motor behaviour of preterm infants
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