Early diagnosis and prognosis in cerebral palsy

Giovanni Cioni, Vittorio Belmonti and Christa Einspieler

The quality of care for the infants born with an extremely low birth weight, or with other conditions of high neurological risk, has achieved extraordinary progress in the last decades. Survival and quality of life have considerably increased for these children, but they still remain at risk for neurological damage, caused by perinatal infections, hypoxic-ischaemic damage, haemorrhagic insult, or by a combination of these factors. Negative outcome includes cerebral palsy (CP), intellectual disability, perceptual and sensory disorders, behavioural disorders and other.

The incidence of CP in particular has been considered the marker of the quality of neonatal care and utilized as an outcome measure in many studies, although cognitive and behavioural problems are by far more common. Those more subtle disorders, which are important for participation and quality of life of the children, are difficult to diagnose in the first weeks or months of life. Conversely, it is largely agreed that an early diagnosis of CP should be possible, or better, should be necessary even in the neonatal period, for a number of reasons.

Although all infants discharged by a neonatal intensive care unit (NICU) and potentially at risk for a neurodevelopmental disorder should enter a follow-up programme, children diagnosed as carrying a risk of CP require medical and social resources that are limited in several countries. Furthermore, an early diagnosis of CP is necessary in order to start early intervention, to tailor it according to the infant’s needs, to modify positively the natural history of her/his condition, and to evaluate the results of the intervention. Randomization of the subjects for early interventional trials, based on neuroprotective drugs, environmental changes, etc., requires detailed prognostic data.

Finally, another major reason for all the efforts made on early diagnosis of CP deals with information in regard to the parents, who obviously ask about the neurodevelopmental outcome of their infants, and their questions are: ‘will he/she be able to walk?’ or ‘to take and use an object?’

Although prognostic hints for a CP diagnosis are needed in the neonatal period, many textbooks and manuals still postpone the possibility of a diagnosis of CP to the end of a so-called ‘silent period’, lasting some weeks or even, for mild forms of CP, some months after term age.

The possibility that neonatal neuroimaging can enable recognition of brain pathology that may lead to a diagnosis of CP is today largely accepted in terms of the type and timing of the brain lesions typical of the different forms of CP (Krägeloh-Mann, 2004), although it is questioned by some authors (O’Shea et al., 1998). A recent paper by de Vries et al. (2011) has unravelled the ‘myth’ that CP cannot be predicted by neonatal neuroimaging, when this technique is correctly applied. The authors show evidence from a number of papers that the non-ambulatory most severe CP can be predicted in the majority of the cases by a combination of sequential brain US and by MRI carried out at term age. Additional useful indices can be obtained by assessing the myelination of the PLIC (posterior limb of internal capsule) and diffusion-weighted imaging techniques. Moreover, there are interesting research directions that may further improve, by sophisticated MRI techniques, the prognostic value of neonatal neuroimaging in the less severe forms of CP.

However, brain MRI in most centres requires the transfer of the infant from the NICU. In addition, the equipment is extremely expensive and therefore not affordable for all centers and countries.

It has also to be remarked that even the most advanced neuroimaging techniques can only show structural changes of the brain and does not provide information on the functional status of the nervous system. For this and other reasons, a clinical assessment is always necessary.

Techniques for the clinical assessment of the neonatal nervous system

Neonatal neurological examination is generally carried out through traditional neurological methods, largely based on muscle tone and neonatal reflexes. However, it is now widely recognized that the human nervous system can express many complex and rapidly changing functions from as early as the first weeks of gestation. Fetuses and newborns are complex organisms producing a great deal of endogenously generated behaviours.

Some of the standard neurological examination methods, though standing as milestones of modern infant neurology, are still influenced by considerations drawn from adult neurology and experiments on animal models. For instance, Saint-Anne Dargassies (1977) developed a pioneering examination protocol based on the evaluation of active and passive tone. Other methods were then proposed in the following decades, including items for muscle tone, postural-motor milestones and, in some cases, behavioural aspects.

The neurological examination protocol proposed in the same period by Prechtl (1977) (not to be confused with the method the same author has later proposed), has been standardized and validated only for the examination of infants at term. It includes the extremely important concept of behavioural states, but many of its items are still based on muscle tone and responses integrated at a low level in the CNS. Moreover, it is rather time-consuming and cannot be applied to preterm infants.

The Neonatal Behavioural Assessment Scale (NBAS) is a technique developed by Brazelton (Brazelton and Nugent, 1995) for examining the behaviour of term infants during the first couple of months of age. Its conceptual basis is founded on the assumption that the newborn has active and specific responses to environmental stimulations, rather than passive behaviour. On the basis of NBAS, Als (1984) standardized a behavioural scale for preterm infants, the Assessment of Preterm Infant Behaviour (APIB), thought to be employed in neonatal intensive care units also for providing and monitoring individualized intervention programmes. These techniques are time-consuming and not easily applicable in clinical settings. Moreover, a high intra-individual day-to-day variability in the responses has been shown for the same test (Sameroff, 1978). Their main applications are in research and early intervention protocols.

Currently, the most recently updated and extensively validated method for the neurological examination of preterm and full-term newborn infants is the Hammersmith Neonatal Neurological Examination (HNNE), first published by Dubowitz and Dubowitz (1981)and updated by Dubowitz et al. (1999). These authors adapted tests drawn from the previous works of Prechtl, Saint-Anne Dargassies and Brazelton, into a simplified and user-friendly pro forma, also including items based on the concepts of Prechtl and co-workers on spontaneous motor activity (see below). The items are organized in six sections: posture and tone; tone patterns; reflexes; movements; abnormal signs; and behaviour. Typical normal and abnormal patterns are extensively described in the manual (Dubowitz et al., 1999) and have proven easily recognizable and clinically useful for diagnosis and prognosis. For research purposes, an optimality score for full-term and preterm newborn infants was also calculated (Mercuri et al., 2003).

On the basis of the neonatal examination, the same authors also developed a protocol for use after the neonatal period in infants up to 24 months of age: the Hammersmith Infant Neurological Examination (HINE) (Dubowitz et al., 1999), divided into three sections: one, non-age-dependent neurological items; a second providing a summary of motor milestones; and a third made of three simple behavioural items. Its prognostic value as to motor outcome has been found high both in preterm infants born before 31 weeks of gestation (Frisone et al., 2002) and in term infants with hypoxic-ischemic encephalopathy (Haataja et al., 2001).

Although both HNNE and HINE have been tested in several clinical and research settings, they also present some limitations. Most items are still correlated with muscle tone and reflexes and the distinction between normal and abnormal patterns may turn out, to some extent, rigid and schematic, hardly comprising the whole complexity of the infant’s repertoire. Moreover, while several studies have reported statistically significant correlations between clinical findings, and mid- and long-term outcome, some others have reported a relevant number of false-positive and false-negative results, especially among preterm infants (see Volpe, 2008, for a review of follow-up studies).

Prechtl’s method on the qualitative assessment of general movements

The basic requirements for an ideal method of neurological assessment for newborn infants were outlined by Heinz Prechtl as follows: it had to be non-invasive, non-time-consuming, and highly sensitive to variations of the age-specific functional repertoire (Prechtl, 1990). None of the traditional protocols of neonatal neurological assessment completely matched these criteria. The observation and categorization of all spontaneous movements in the first months of life led Prechtl and his co-workers to the identification of several normal and abnormal motor patterns. Among others, the so-called ‘general movements’ (GMs) were identified as on-going global movements involving all body parts and appeared particularly suitable for assessment (Prechtl, 1990, 2001). This gave birth to Prechtl’s Method on the Qualitative Assessment of General Movements in Preterm, Term and Young Infants (see the published handbook: Einspieler et al., 2004).

Though based on global and qualitative judgement, GM assessment has proven a very sound method. Its validity and reliability have been extensively evaluated in a number of studies, mainly dealing with the prediction of CP (Cioni et al., 2000; Ferrari et al., 2002; Prechtl, 1997), but also with that of minor neurological disorders (Bruggink et al., 2008; Einspieler et al., 2007; Groen et al. 2005), Rett syndrome (Einspieler et al., 2005a,b), cognitive development (Bruggink et al., 2010) and autistic spectrum disorders (Phagava et al., 2008).

Normal GMs involve the whole body in a complex sequence of arm, leg, neck and trunk movements. They wax and wane in intensity, force and speed, and have a gradual beginning and end. Rotations along the axis of the limbs and slight changes in the direction of movement make them fluent and elegant and create the impression of complexity and variability. GMs appear as early as nine to 12 weeks postmenstrual age (PMA) and continue after birth without substantially changing their form until 46 to 49 weeks PMA, irrespective of when birth occurs. At 46 to 49 weeks PMA, a major change in form sets in, being fulfilled around 3 months post-term, when the so-called fidgety movements (FMs) appear (Hadders-Algra and Prechtl, 1992; Prechtl, 1990). From 5 to 6 months post-term, GMs fade out, while new, voluntary motor patterns emerge.

Though complex and variable by definition, GMs can be classified into a limited number of recognizable patterns, related to PMA and either normal or abnormal. Normal GMs are briefly reported in Table 8.1.

Table 8.1

Description of normal and abnormal general movement patterns