VicCPchild- Prospective Cohort Study Of Children With Cerebral Palsy
Funder
National Health and Medical Research Council
Funding Amount
$613,587.00
Summary
Cerebral palsy is the most common cause of physical disability in children affecting 1 in 500 young Australians. While the brain lesion is static, the musculoskeletal problems are progressive and require lifelong management (cost of US$946,000 over life per person). Only large prospective population-based studies give a true indication of the incidence of physical problems, determine the pathway(s) to outcome and determine the best pathways to successful treatment and efficient resource allocati ....Cerebral palsy is the most common cause of physical disability in children affecting 1 in 500 young Australians. While the brain lesion is static, the musculoskeletal problems are progressive and require lifelong management (cost of US$946,000 over life per person). Only large prospective population-based studies give a true indication of the incidence of physical problems, determine the pathway(s) to outcome and determine the best pathways to successful treatment and efficient resource allocation. The broad aim of this project is: This population based cohort study (n - 240) aims to determine the pathway to motor outcome from diagnosis at 18 months to 5 years based on the nature of the brain injury at 24 months (structural MRI of the nature, location and timing of the brain lesion). Secondary Aims: Determine the rate of musculoskeletal deformity (hip displacement, spasticity, muscle contracture). Potential impact of medical co-morbidities (nutrition, epilepsy, respiratory problems) Patterns of participation and HRQOL. Patterns of medical resource use: treatment costs and outcomes. This study will: Allow clinicians to better the likely functional outcomes of children with CP from an earlier age based on the rate and limit of gross motor development and nature and severity of the brain lesion, determine the nature and timing of physical deformities to aid prevention and treatment; provide information on resource use for future planning and organisation of medical and therapy services. This in turn will give more accurate prognostic counseling as well as target areas for early therapy. Our multidisciplinary research group is uniquely placed to conduct this world-first study with access to two entire birth years of children linked to our Victorian Cerebral Palsy Register. Recruitment is conducted at both the Royal Children's Hospital and the Monash Medical centre in order to ensure state wide referral and easy access for families.Read moreRead less
A Genomic Basis For Cerebral Palsy - Studies On A Large Australian Cohort
Funder
National Health and Medical Research Council
Funding Amount
$518,305.00
Summary
Cerebral Palsy (CP) is the commonest neurological disability in children, affecting 1 in every 500 children. This research will investigate genetic causes of CP by testing families with and without CP for a range of genetic alterations that change fetal protection to inflammation with resultant brain damage and CP. Research in to the causes of CP will allow prevention strategies to be developed, to ultimately reduce social and financial costs of CP for the patient, their family and the community ....Cerebral Palsy (CP) is the commonest neurological disability in children, affecting 1 in every 500 children. This research will investigate genetic causes of CP by testing families with and without CP for a range of genetic alterations that change fetal protection to inflammation with resultant brain damage and CP. Research in to the causes of CP will allow prevention strategies to be developed, to ultimately reduce social and financial costs of CP for the patient, their family and the community.Read moreRead less
Mechanisms Guiding Pathfinding And Positioning Of Cortical Interneurons
Funder
National Health and Medical Research Council
Funding Amount
$621,606.00
Summary
Brain disorders place an economic and social burden on Australia and the personal costs of these illnesses are immeasurable. Several brain abnormalities are caused from the failure of neurons to position themselves in the correct location when the brain develops. Our study aims to discover how neurons move and what factors influence this process. It provides an understanding of normal brain development, as well as providing insight into what may go wrong in the formation of brain diseases.
The Role Of Reelin-signalling On Cortical Neuron Migration
Funder
National Health and Medical Research Council
Funding Amount
$716,196.00
Summary
Disorders that occur during brain development can lead to abnormal behaviours traits such as anxiety and altered social interactions, plus abnormalities in neuronal function and information processing. The region of the brain responsible for originating the motor, sensory and cognitive functions of a human is the cortex. This brain region is comprised of two major types of neurons that are arranged in a highly organized manner. One captivating aspect of the brain is that during early stages of d ....Disorders that occur during brain development can lead to abnormal behaviours traits such as anxiety and altered social interactions, plus abnormalities in neuronal function and information processing. The region of the brain responsible for originating the motor, sensory and cognitive functions of a human is the cortex. This brain region is comprised of two major types of neurons that are arranged in a highly organized manner. One captivating aspect of the brain is that during early stages of development neurons are generated in one part of the brain and migrate great distances to a final destination. It is therefore necessary during development to have a well-orchestrated, controlled series of events that lead to the correct positioning and association of neurons. The precise functions of many gene products involved in this process are not known. One major advancement in the development of the cortex is the discovery of the protein Reelin which is found in the outermost region of the developing cortex. Mutations in Reelin, in humans, have been implicated in the causation of schizophrenia and mood disorders. These disease states are the result of altered migration of neurons in the cortex. The research proposed in this application is designed to understand the precise process of how two types of neurons migrate and assemble in the cortex. Technology today allows us to visualize, in culture, neurons as they migrate in real-time. This is referred to real time-lapse imaging and allows the researcher the ability to examine how external factors, affect migration of cortical neurons. We will determine how Reelin is involved in this process and our research will elucidate the fundamental process of cortical brain development.Read moreRead less
The Effect Of Very Premature Birth On Brain Development
Funder
National Health and Medical Research Council
Funding Amount
$517,975.00
Summary
The neurological outcome of the premature infant is of major importance. Approximately 2,600 premature infants weighing less than 1500 grams are born annually in Australasia. Of the approximate 2,400 survivors between 5-15% will have a more major cerebral palsy, i.e. around 200 children per annum. A greater proportion of 25-50%, i.e., upto 1200 children will have a developmental disability that will adversely affect their school perfomance requiring special assistance or repeating grades. With a ....The neurological outcome of the premature infant is of major importance. Approximately 2,600 premature infants weighing less than 1500 grams are born annually in Australasia. Of the approximate 2,400 survivors between 5-15% will have a more major cerebral palsy, i.e. around 200 children per annum. A greater proportion of 25-50%, i.e., upto 1200 children will have a developmental disability that will adversely affect their school perfomance requiring special assistance or repeating grades. With an increasing number of very prematurely born infants surviving, the absolute number of affected children will continue to rise. Prevention of these disabilities will require an understanding of the cause. The educational and social implications of these high rates of neuro-developmental disability are enormous and the focus of wide international concern. Magnetic Resonance Imaging : It is a major challenge for neonatologists to be able to understand the impact of their therapies and managements on the developing brain. A window into the newborn brain can be seen utilising advanced magnetic resonance imaging techniques in-vivo to investigate these key issues: 1. What is the nature of brain injury in the prematurely born infant? 2. What are the risk factors for brain injury in the prematurely born infant - and are they able to be altered to reduce this risk - e.g. blood pressure management, steroid therapy 3. Is the brain of a prematurely born infant different from that of a full term born infant at TERM equivalent - if so, how is it different? 4. Are there certain postnatal therapies that relate to any alteration in brain structure and chemistry - e.g. postnatal nutrition, modes of ventilation, pharmacological therapies? 5. How does the brain structure relate to function on long term neuro-developmental follow up of our infants at 2 years?Read moreRead less
The Role Of Rnd Genes During Cortical Neurogenesis And Cell Migration
Funder
National Health and Medical Research Council
Funding Amount
$410,384.00
Summary
In order for the brain to function properly, tens of billions of neurons within it first have to be born, then find their proper location before connecting with other neurons in a highly ordered fashion. Failure of these key processes heavily impacts on subsequent brain function, and have been shown to underlie several disorders including epilepsy. This study will investigate how members of the Rnd gene family control cell production and positioning within the developing brain.
Improving The Outcome Of Premature Infants- A Randomised Trial Of Preventive Care At Home
Funder
National Health and Medical Research Council
Funding Amount
$633,375.00
Summary
The high rate of adverse neurodevelopmental outcomes of very premature infants is of major concern. In Australia there are approximately 2600 very low birthweight (VLBW, birthweight <1500 g) or very premature (<30 weeks' gestational age) survivors per annum. A large proportion of these infants (40%-50%) will later develop motor incoordination, cognitive impairment, attention deficits or behavioural problems (up to 1300 new cases per year). There is little research to test the efficacy of e ....The high rate of adverse neurodevelopmental outcomes of very premature infants is of major concern. In Australia there are approximately 2600 very low birthweight (VLBW, birthweight <1500 g) or very premature (<30 weeks' gestational age) survivors per annum. A large proportion of these infants (40%-50%) will later develop motor incoordination, cognitive impairment, attention deficits or behavioural problems (up to 1300 new cases per year). There is little research to test the efficacy of early preventive care programs geared to changing the infant's environment (physical management, behavioural regulation, maternal factors). In the proposed study we aim to use a low cost preventive care program at home conducted by physiotherapists and psychologists that has been shown to have utility and efficacy in pilot work, with follow up until 2 years of age. In subsequent studies we would aim to follow this cohort to school age, to determine if there are any lasting benefits of early intervention accompanied by measures of brain growth and structural development using advanced imaging techniques. Any new health care program should result not only in improvements in health, but should be affordable to implement so an economic evaluation will also be undertaken. This study will also utilise novel and advanced MRI brain imaging techniques to understand the complex interaction between brain injury and altered brain development in these infants with the risk and the repsonse to this program of care. In this way the changes in brain connectivity, structure and biochemistry can be formally defined to undertsnad the pathway of any potential benefit from this program.Read moreRead less
Blood-brain Barrier And White Matter Damage In The Immature Rat Brain Following Systemic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$353,173.00
Summary
Clinical obstetric and paediatric studies have identified an association between intrauterine infection occurring around two thirds of the way through pregnancy, premature birth and a specific form of damage to the brain of the newborn. This damage mainly affects white matter tracts. These tracts are aggregations of nerve fibres that make the connections between different parts of the brain and may result in cerebral palsy or other neurological disorders. The association between maternal infecti ....Clinical obstetric and paediatric studies have identified an association between intrauterine infection occurring around two thirds of the way through pregnancy, premature birth and a specific form of damage to the brain of the newborn. This damage mainly affects white matter tracts. These tracts are aggregations of nerve fibres that make the connections between different parts of the brain and may result in cerebral palsy or other neurological disorders. The association between maternal infection and brain damage, one form of which is cerebral palsy, is well established from clinical epidemiological studies, but the biological mechanism of this link is unknown. The CIs' group has recently shown that the condition can be reproduced in neonatal rats at a stage of brain development in the rat that is equivalent to the critical time in human brain development when infection may be associated with brain damage. The CIs' group has shown that an induced inflammatory state similar to a bacterial infection, results in damage to blood vessels in the white matter and is associated with changes in white matter, as occurs in affected babies. The purpose of this study is to understand the nature of the damage to white matter blood vessels and the mechanisms by which materials in blood, which in the normal brain do not pass from the blood to the brain across the blood-brain barrier, are able to do so via the inflammation damaged blood vessels. The study also aims to show whether it is components of the blood entering the brain via the damaged blood vessels that are responsible for the damage to white matter in the immature brain. The outcome should lead to development of ways to improve clinical care of women who acquire infections during pregnancy.Read moreRead less
Mechanisms Controlling Interneuron Migration And Layering In The Cortex
Funder
National Health and Medical Research Council
Funding Amount
$613,060.00
Summary
This work will increase our understanding of how the brain is assembled and what mechanisms control this process. Understanding this highly orchestrated string of events is vital as abnormal positioning and numbers of neurons are known pathologies in brains of patients with epilepsy and schizophrenia. Using state of the art equipment we can visualize neurons moving in brain slices in real-time and investigate environmental factors involved in this important process.