Giovanni Cioni

Qualitative changes of general movements in preterm infants with brain lesions

The aims of the study were (1) to replicate previous quantitative studies of motor activity in low-risk and high-risk preterm infants and (2) to apply a new method of systematic analysis of the qualitative characteristics of general movements in these two groups of infants. Sequential one-hour videorecordings of the unstimulated infants in the incubator were made during the preterm period and then continued during the postterm period until about 20 weeks. The high-risk group consisted only of infants with signs of haemorrhage and/or leucomalacia in the repeated ultrasonograms of the brain. The neurological follow-up continued up to a minimum of one and a maximum of three years of corrected age. The quantification of the various motor patterns in 12 matched pairs of low-risk and high-risk preterm infants revealed a slight but significant (P = 0.05) excess of isolated arm movements in the low-risk cases during the activity phase. No other movement pattern differed significantly. The qualitative assessment of general movements during the preterm period resulted in all but one of the 14 low-risk cases having a normal quality of general movements. In the lesion-group (N = 29) all the infants had an abnormal quality during the preterm period. Eight cases later became neurologically normal although 1 of them had strabism. In addition, one infant was blind (ROP) and retarded and one other had mental retardation. Nineteen infants later developed cerebral palsy (two monoplegia of a leg, three hemiplegia, 5 diplegia and 9 quadriplegia). Strabism was present in 48.3% of the whole group of 29 cases. A semi-quantitative estimation of various aspects of the abnormal general movements made a typology of abnormal patterns possible. A graphic display of developmental trajectories of individual cases, depicting the course of abnormal aspects along the time axis, helps document the evolution of abnormal signs. Their course is a better predictor of the neurological outcome than the nature and localization of the lesion, detected by imaging techniques. The qualitative assessment of general movements from videorecordings is a reliable, quick, cheap and totally non-intrusive method in neonatology for the early detection of functional impairment of the nervous system.

Is hemiplegic cerebral palsy equivalent to amblyopia of the corticospinal system

Subjects with severe hemiplegic cerebral palsy have increased ipsilateral corticospinal projections from their noninfarcted cortex. We investigated whether their severe impairment might, in part, be caused by activity‐dependent, competitive displacement of surviving contralateral corticospinal projections from the affected cortex by more active ipsilateral corticospinal projections from the nonaffected cortex, thereby compounding the impairment.

Arginine:Glycine Amidinotransferase Deficiency: The Third Inborn Error of Creatine Metabolism in Humans

Arginine:glycine amidinotransferase (AGAT) catalyzes the first step of creatine synthesis, resulting in the formation of guanidinoacetate, which is a substrate for creatine formation. In two female siblings with mental retardation who had brain creatine deficiency that was reversible by means of oral creatine supplementation and had low urinary guanidinoacetate concentrations, AGAT deficiency was identified as a new genetic defect in creatine metabolism. A homozygous G-A transition at nucleotide position 9297, converting a tryptophan codon (TGG) to a stop codon (TAG) at residue 149 (T149X), resulted in undetectable cDNA, as investigated by reverse-transcription PCR, as well as in undetectable AGAT activity, as investigated radiochemically in cultivated skin fibroblasts and in virus-transformed lymphoblasts of the patients. The parents were heterozygous for the mutant allele, with intermediate residual AGAT activities. Recognition and treatment with oral creatine supplements may prevent neurological sequelae in affected patients.

The qualitative assessment of general movements in preterm, term and young infants — review of the methodology

We describe the state of the art of Prechtls method for the qualitative assessment of general movements as a diagnostic tool for early detection of brain dysfunction. After discussing the optimal technique for video recording general movements in preterm, term and young infants, attention is focused on the proper analysis of this spontaneous motor pattern. Recently, a group of active researchers in the field reached consensus on the various qualities of normal and abnormal general movements. These definitions are reported here in full. Since it is a newly introduced method careful investigation into its reliability is required. Various groups of investigators have obtained data which demonstrate the robust character of the method (interscorer agreement: 78-98%). Finally, we discuss the validity of this early assessment method on the basis of the reports published so far. While the methods sensitivity is similar in all age groups studied (preterm, term, first month, second month, and third month age epochs), and averages 94.5%, the specificity of the method is age-dependent. It is low during the early ages, increases gradually and reaches 82 to 100% at 3 months post-term. This phenomenon is explained by spontaneous recovery of early dysfunction. In contrast, consistent abnormalities of general movements are linked to neurological deficits found at the 2 year follow-up.

Dorsal and ventral stream sensitivity in normal development and hemiplegia

Form and motion coherence thresholds can provide comparable measures of global visual processing in the ventral and dorsal streams respectively. Normal development of thresholds was tested in 360 normally developing children aged 4–11 and in normal adults. The two tasks showed similar developmental trends, with some greater variability and a slight delay in motion coherence compared to form coherence performance, in reaching adult levels. To examine the proposal of dorsal stream vulnerability related to specific developmental disorders, we compared 24 children with hemiplegic cerebral palsy with the normally developing group. Hemiplegic children performed significantly worse than controls on the motion coherence task for their age, but not on the form coherence task; however, within this group no specific brain area was significantly associated with poor motion compared to form coherence performance. These results suggest that extrastriate mechanisms mediating these thresholds normally develop in parallel, but that the dorsal stream has a greater, general vulnerability to early neurological impairment.

Massage Accelerates Brain Development and the Maturation of Visual Function

Environmental enrichment (EE) was shown recently to accelerate brain development in rodents. Increased levels of maternal care, and particularly tactile stimulation through licking and grooming, may represent a key component in the early phases of EE. We hypothesized that enriching the environment in terms of body massage may thus accelerate brain development in infants. We explored the effects of body massage in preterm infants and found that massage accelerates the maturation of electroencephalographic activity and of visual function, in particular visual acuity. In massaged infants, we found higher levels of blood IGF-1. Massage accelerated the maturation of visual function also in rat pups and increased the level of IGF-1 in the cortex. Antagonizing IGF-1 action by means of systemic injections of the IGF-1 antagonist JB1 blocked the effects of massage in rat pups. These results demonstrate that massage has an influence on brain development and in particular on visual development and suggest that its effects are mediated by specific endogenous factors such as IGF-1.

Preterm and early postterm motor behaviour in low-risk premature infants

The development of spontaneous motility and posture was studied longitudinally in 14 carefully selected low-risk preterm infants. The aim of this investigation was to provide a set of data suitable for comparison with fetuses and with neurologically abnormal preterm infants. The infants were videorecorded weekly, for one hour in a supine position, from birth until their discharge from the hospital. Ten of them were thereafter also observed at home at 3-week intervals from 3 to 18 weeks of corrected age, together with 10 healthy fullterm infants. Occurrence and duration of motor patterns and postures in periods of rest and activity were obtained by off-line analysis of the videotapes. Few significant changes were found from birth until term age in the composition and quantity of the spontaneous movement patterns. Only twitches and stretches during activity periods showed a small decline approaching term age. However, notable inter-individual differences and intra-individual fluctuations from week to week were observed. Postterm development of preterm infants was similar to that of the fullterms. Both showed considerable changes in the qualities of general movements after the first postterm weeks. Only fidgety character movements occur earlier in preterm infants. No age-specific preference postures of the limbs were found in the preterm period. Midline position of the head in supine was observed at about the same postterm age in preterm and fullterm groups. Asymmetrical tonic neck postures were very inconsistently present before term age and rapidly disappeared after term, earlier so in preterm infants.

Comparison between observation of spontaneous movements and neurologic examination in preterm infants

OBJECTIVE The Prechtl method of qualitative assessment of general movements (GMs) has been shown to be a good predictor of neurologic outcome in fetuses, preterm infants, and term infants. The aim of this study was to compare the results of this new technique with those of traditional neurologic examination and of cranial ultrasonography in preterm infants. METHODS Serial videotape recordings (with off-line assessment of GMs), ultrasound examination of the brain, and neurologic examinations were performed from birth until about 6 months of corrected age, on a group of 66 preterm infants whose gestational age ranged from 26 to 36 weeks (mean 30.7 weeks). The agreement between the two techniques and their predictive power, with respect to the neurologic outcome at 2 years of corrected age, were evaluated for five different age groups from preterm age to 65 weeks of postmenstrual age. RESULTS Overall agreement of the neurologic and GM findings was 80.3% and strongly age related (lower during the preterm and term periods and higher thereafter). At all ages the results of GM observation correlated highly with neurologic outcome; they showed higher sensitivity and specificity than the neurologic examination. This held true in particular before term age, when poor neurologic responses might be related to transient complications, and at term age, mainly because of infants with normal neurologic examination results but unfavorable outcome. During the preterm period the ultrasound results showed a better specificity and a lower sensitivity to outcome than GM findings. CONCLUSIONS The results of this study indicate that quality assessment of GMs should be added to traditional neurologic assessment, neuroimaging, and other tests of preterm infants for diagnostic and prognostic purposes.

Cerebral visual impairment in preterm infants with periventricular leukomalacia

Neonatal brain lesions are the main cause of cerebral visual impairment in infancy, i.e., of a visual deficit caused by damage to posterior visual pathways. Visual outcome of preterm infants with periventricular leukomalacia (PVL) was investigated in 14 subjects affected by severe cystic PVL, another 34 with moderate PVL (prolonged periventricular echodensities), and 18 control preterm infants. All cases with significant ocular abnormalities (such as retinopathy of prematurity state III or upwards, optic nerve atrophy, or major refraction problems) were excluded. Visual acuity, visual field, eye alignment, fixation and following, optokinetic nystagmus, and visual threat were tested at 1 year of corrected age. A high incidence of cerebral visual impairment, consisting mainly of low visual acuity, severe oculomotor disorders, and reduced visual field, was found in infants with severe PVL. Visual defects were less frequent and less severe in the moderate PVL group, and very rare in the control group. The results of neuroimaging, and especially of magnetic resonance imaging, correlated with the visual outcome and indicate lesions at the level of optic radiations as the main anatomic substrate of the visual impairment. All infants with PVL need a visual follow-up, from the first months of life, the results of which are important both for visual and motor rehabilitation of these cases and for their daily care.

Plasticity and Reorganization During Language Development in Children with Early Brain Injury

Although some studies have reported subtle language deficits following early focal brain lesions (EFBL), most studies find no evidence for differential language outcomes as a function of lesion side or lesion type in children with congenital injuries to one side of the brain. However, recent prospective studies of the first stages of language development in English-speaking children with EFBL have reported greater delays in expressive vocabulary in children with left-hemisphere damage, particularly if the lesion involves left temporal cortex. In the present study, first stages in the development of word production were studied in 43 Italian children with congenital EFBL, between 13 and 46 months of age. As a group, the EFBL children were markedly delayed in expressive vocabulary. Among children who were in the first stage of language learning, delays were significantly greater with left-hemisphere injury. However, this left-right difference was not evident in children who had moved on to the next stage of language development, producing at least some sentences. Discussion centers on the role of developmental plasticity in determining the outcomes of early focal brain injury, suggesting that recovery from initial delays may take place in the early stages of language development, at least for some children.