Andrea Guzzetta

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.

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.

Correlation between visual function, neurodevelopmental outcome, and magnetic resonance imaging findings in infants with periventricular leucomalacia

AIM To evaluate the correlation between visual function and neurodevelopmental outcome in children with periventricular leucomalacia at 1 and 3 years. METHOD Visual acuity, visual field, ocular motility, and optokinetic nystagmus were tested in 29 infants with periventricular leucomalacia by brain magnetic resonance imaging. All infants also had a structured neurological examination and a Griffiths developmental assessment. RESULTS 21 of the infants showed at least one abnormality of visual function. The degree of visual impairment—that is, the number of visual tests showing abnormal results—correlated well with the results on developmental assessment at both ages. CONCLUSION Multivariate analysis showed that visual impairment was the most important variable in determining the neurodevelopmental scores of these infants, more than their motor disability and the extent of their lesions on magnetic resonance imaging.

MRI Structural Connectivity, Disruption of Primary Sensorimotor Pathways, and Hand Function in Cerebral Palsy

Brain injury and subsequent plasticity of sensory and corticospinal pathways play an integral role in determining paretic hand function in congenital hemiplegia. There is limited knowledge regarding the relationship between the disruption of sensorimotor thalamic pathways projecting into the primary motor cortex and motor control. This study sought to investigate the relationship between the structural connectivity of motor networks that anatomically link the brain stem with the precentral and postcentral gyri with paretic motor sensory function by using an automated analysis strategy. Magnetic resonance imaging structural connectivity was measured by using high-angular-resolution diffusion imaging, probabilistic tractography, and the anatomic parcellation of high-resolution structural images in 16 children with congenital unilateral periventricular white-matter damage. Connectivity of the corticospinal and corticothalamic pathways was determined by using an asymmetry index based on the number of streamlines contained within these projections and compared with measures of paretic hand function and bimanual coordination. For cortical development, the volume of the ipsilesional precentral gyrus was significantly reduced. For connectivity measures, the numbers of streamlines in corticospinal tracts and corticothalamic pathways within the ipsilesional hemisphere were decreased compared with the contralesional side. The sensorimotor thalamic projections were more significantly correlated with paretic hand functions than were the corticospinal tracts. These data support the concept that preservation of sensorimotor thalamic pathways that directly project into the primary motor cortex has more influence on motor function control of the paretic hand than does preservation of corticospinal tracts.

Visual function in term infants with hypoxic-ischaemic insults: correlation with neurodevelopment at 2 years of age

AIMS To determine if there is any association between the findings of visual assessment performed at the age of 5 months and neurodevelopmental outcome at the age of 2 years in children who have sustained hypoxic-ischaemic insults. METHODS Twenty nine term infants with hypoxic–ischaemic encephalopathy and/or brain lesions on neonatal magnetic resonance imaging (MRI) were prospectively evaluated. At 5 months of age all the infants had their visual function assessed using the Atkinson Battery of Child Development for Examining Functional Vision, which includes the assessments of optokinetic nystagmus (OKN), acuity, visual fields, fixation shift and phase and orientation reversal visual evoked potentials. At 2 years of age the children had a structured neurological evaluation and a Griffiths developmental assessment. RESULTS There was good correlation between the extent of the early detected visual impairment and both neuromotor and global development. Children with more than three out of five abnormal visual tests at 5 months of age tended to have abnormal neurological examination results and abnormal developmental quotients. Children with three or fewer abnormalities tended to have developmental quotients in the normal range; the level of their performance, however, was still related to the number of visual tests passed. CONCLUSIONS Individual visual tests can provide important prognostic information. While abnormal OKN and acuity were always associated with abnormal outcome, normal results on visual evoked potentials and fixation shift tended to be associated with normal outcome.

The effects of preterm infant massage on brain electrical activity

Aim  Early intervention programmes based on the manipulation of the extra‐uterine environment have been used in preterm infants with the aim of improving development and functional outcome. Infant massage, among them, has proved effective for weight gain and reduced length of stay in the neonatal intensive care unit. We have recently shown that infant massage accelerates brain maturation of low‐risk preterm infants without brain abnormalities as measured by global parameters of electroencephalography (EEG) activity. In the present study we further analyse the same cohort of preterm infants, testing the hypothesis that massage determines changes in EEG spectral activity, a highly sensitive index of brain maturation.

Brain representation of active and passive hand movements in children.

Several functional neuroimaging studies have been performed exploring the sensorimotor function in children with neurologic disorders. However, little is known about normal activation patterns of the sensorimotor system at a young age. We explored brain representation of active and passive hand movements in school-age children and young adults. Nine healthy children (7–15 y) and six adults were studied. Functional magnetic resonance imaging (fMRI) data were acquired on a 1.5-T scanner in block designs. Active movement consisted of repetitive opening and closing of the hand; passive movement consisted of the same movement performed by the examiner. Both hands were assessed separately. The pattern of brain activation (contralateral primary sensorimotor cortex (SMC), ipsilateral cerebellum, supplementary motor area (SMA), and lateral premotor cortex (PMC) was generally more widespread in the adult group, suggesting a developmental course in the organization of both motor and sensory cortex. Surprisingly, no difference was generally detected when contrasting active versus passive tasks. Our results suggest that active and passive hand movements can be used for the exploration of the sensorimotor system in children. Passive and active tasks confirmed to be tightly coupled, thus supporting the idea of the former as a helpful performance-independent paradigm in the study of brain reorganization and presurgical assessment.

Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy: Advances in Diagnosis and Treatment

Importance Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months’ corrected age. Objectives To systematically review best available evidence for early, accurate diagnosis of cerebral palsy and to summarize best available evidence about cerebral palsy–specific early intervention that should follow early diagnosis to optimize neuroplasticity and function. Evidence Review This study systematically searched the literature about early diagnosis of cerebral palsy in MEDLINE (1956-2016), EMBASE (1980-2016), CINAHL (1983-2016), and the Cochrane Library (1988-2016) and by hand searching. Search terms included cerebral palsy, diagnosis, detection, prediction, identification, predictive validity, accuracy, sensitivity, and specificity. The study included systematic reviews with or without meta-analyses, criteria of diagnostic accuracy, and evidence-based clinical guidelines. Findings are reported according to the PRISMA statement, and recommendations are reported according to the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument. Findings Six systematic reviews and 2 evidence-based clinical guidelines met inclusion criteria. All included articles had high methodological Quality Assessment of Diagnostic Accuracy Studies (QUADAS) ratings. In infants, clinical signs and symptoms of cerebral palsy emerge and evolve before age 2 years; therefore, a combination of standardized tools should be used to predict risk in conjunction with clinical history. Before 5 months’ corrected age, the most predictive tools for detecting risk are term-age magnetic resonance imaging (86%-89% sensitivity), the Prechtl Qualitative Assessment of General Movements (98% sensitivity), and the Hammersmith Infant Neurological Examination (90% sensitivity). After 5 months’ corrected age, the most predictive tools for detecting risk are magnetic resonance imaging (86%-89% sensitivity) (where safe and feasible), the Hammersmith Infant Neurological Examination (90% sensitivity), and the Developmental Assessment of Young Children (83% C index). Topography and severity of cerebral palsy are more difficult to ascertain in infancy, and magnetic resonance imaging and the Hammersmith Infant Neurological Examination may be helpful in assisting clinical decisions. In high-income countries, 2 in 3 individuals with cerebral palsy will walk, 3 in 4 will talk, and 1 in 2 will have normal intelligence. Conclusions and Relevance Early diagnosis begins with a medical history and involves using neuroimaging, standardized neurological, and standardized motor assessments that indicate congruent abnormal findings indicative of cerebral palsy. Clinicians should understand the importance of prompt referral to diagnostic-specific early intervention to optimize infant motor and cognitive plasticity, prevent secondary complications, and enhance caregiver well-being.

Australian Cerebral Palsy Child Study Protocol of a prospective population based study of motor and brain development of preschool aged children with cerebral palsy

BackgroundCerebral palsy (CP) results from a static brain lesion during pregnancy or early life and remains the most common cause of physical disability in children (1 in 500). While the brain lesion is static, the physical manifestations and medical issues may progress resulting in altered motor patterns. To date, there are no prospective longitudinal studies of CP that follow a birth cohort to track early gross and fine motor development and use Magnetic Resonance Imaging (MRI) to determine the anatomical pattern and likely timing of the brain lesion. Existing studies do not consider treatment costs and outcomes. This study aims to determine the pathway(s) to motor outcome from diagnosis at 18 months corrected age (c.a.) to outcome at 5 years in relation to the nature of the brain lesion (using structural MRI).MethodsThis prospective cohort study aims to recruit a total of 240 children diagnosed with CP born in Victoria (birth years 2004 and 2005) and Queensland (birth years 2006–2009). Children can enter the study at any time between 18 months to 5 years of age and will be assessed at 18, 24, 30, 36, 48 and 60 months c.a. Outcomes include gross motor function (GMFM-66 & GMFM-88), Gross Motor Function Classification System (GMFCS); musculoskeletal development (hip displacement, spasticity, muscle contracture), upper limb function (Manual Ability Classification System), communication difficulties using Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS-DP), participation using the Paediatric Evaluation of Disability Inventory (PEDI), parent reported quality of life and classification of medical and allied health resource use and determination of the aetiology of CP using clinical evaluation combined with MRI. The relationship between the pathways to motor outcome and the nature of the brain lesion will be analysed using multiple methods including non-linear modelling, multilevel mixed-effects models and generalised estimating equations.DiscussionThis protocol describes a large population-based study of early motor development and brain structure in a representative sample of preschool aged children with CP, using direct clinical assessment. The results of this study will be published in peer reviewed journals and presented at relevant international conferences.Trial registrationAustralia and New Zealand Clinical Trials Register (ACTRN1261200169820)