Category Archives: Research

Towards a real impact on prenatal brain damage

Brain tractography

Brain tractography

We take a look at the pioneering work of the Cerebra Foetal Research Project at the University of Barcelona.

The human brain undergoes a long phase of development that starts in foetal life and ends much later in life. The most critical steps take place in the mother’s womb and during the first two years of life. Millions of neurons are being generated every day and start establishing connections, determining how our brain is going to work for the rest of our lives. This extremely complex process is governed by information contained in our genes, but also by the environment. Any disturbance may have a critical influence in the delicate sequence of events regulated in the genetic blueprint.

One in ten children has neurodevelopmental problems. It is estimated that about two thirds of these are of prenatal origin and in most instances, the problem occurred during foetal life, long before labour started. Severe forms of brain damage affect about 2/1000 of all new-borns and are expressed by serious complications including cerebral palsy and/or intellectual disability.

The vast majority of brain problems however, are manifested as subtle developmental disturbances. These cases are not associated with overt brain injury, but with brain reorganisation and are expressed mainly as alterations in cognition, thus affecting behaviour, social relations, neuromuscular regulation, learning and memory. The impact of these ‘milder’ neurological alterations in the quality of life cannot be overemphasized. Because they are of milder nature, they mostly go unnoticed in early months and even years of life.

Identification

Identification of foetal brain injury/reorganisation as early as possible is a major opportunity for public health. The problem involves thousands of families yearly. For the first two years of life, the growing brain has enough plasticity (the brain’s ability to respond and remodel itself) to bring back to normal deviations that occurred during intrauterine life. This has been defined as the ‘window of opportunity’ to revert the effects of in utero diseases on foetal programming.

Unfortunately, early diagnosis is still not possible in a substantial majority of cases. Much is still unknown about how a developing foetal brain adapts to and eventually deteriorates under adverse conditions. We need to improve the understanding and current diagnostic means of perinatal brain injury if we hope to start early interventions.

The list of foetal problems potentially leading to brain injury is large, but the majority of cases are caused by prematurity and intrauterine growth restriction (IUGR). Over the last 10 years the team in Barcelona has worked on both, but have focused more on IUGR as there was much less known about this disease and the opportunities for public health were greater.

Intrauterine Growth Restriction & Prematurity

IUGR is normally the consequence of placental insufficiency. The placenta is the organ that the foetus uses to obtain nutrients and oxygen from the mother. In a proportion of pregnancies, for a variety of reasons, the placenta does not grow properly and is not able to satisfy the enormous requirements of the foetus. In these circumstances, the ‘genetic program’ can not build the brain in the way it was supposed to, so that reprogramming, and consequently reorganization, must occur.

In prematurity, which is typically characterised by intrauterine infection, the baby is exposed to the ‘outer world’ when its brain is still in the critical construction phase. Changes in temperature, feeding, sound and light have, as of yet, unknown effects on the developing brain.

Cerebra Foetal Research Programme

The Cerebra Foetal Research Programme incorporates a variety of projects that aim to diagnose abnormal brain development in foetuses and new-borns, and implement specific interventions to prevent, or reduce its impact. The main interrelated research lines cover problems of maternal, foetal and neonatal health, and are summarised below.

Brain Connectivity

The main objective of this research line is to develop a quantitative imaging biomarker for early diagnosis of neurodevelopmental disorders based on the imaging of the brain connectivity (the way neurons connect the different brain areas). To accomplish that, different techniques of Magnetic Resonance Imaging (MRI) are being used, including diffusion, functional and anatomical MRI.

Neurological Programming (Microstructure and Metabolomics)

In this research line, the group focuses on identifying the structural (the way neurons and other cells are organised within the brain microscopically) and metabolic differences in the brain of foetuses and children that are diagnosed with growth restriction and are at risk of developing neurodevelopmental problems. This requires the development of new mathematical algorithms that will allow the interpretation of subtle brain changes that could be used as new biomarkers.

Diagnosis and Therapy in IUGR

This line of research aims to identify before birth, which babies with growth problems will have abnormal neurodevelopment. The majority of babies considered small in utero are naturally smaller and will face no future problems. However, a proportion of babies are born small due to problems with the placenta. These babies face neurobehavioral problems at birth that persist into childhood.

The Foetal Medicine Research Centre has developed non-invasive methods to measure how much blood reaches the brain, and have described that this is a strong marker of increased risk for neurodevelopmental problems. The prenatal identification of babies at risk is especially important because it would allow us to take preventive measures during pregnancy and early childhood.

Prematurity

The main objective of this line of research on prematurity is to advance our knowledge of the causes of preterm birth. Despite improvements in managing pregnancy, prematurity is still a common outcome and is the leading cause of perinatal morbidity and mortality. It is crucial to understand what triggers premature delivery so that we can prevent it and improve perinatal outcomes.

The Foetal Medicine Research Centre is trying to refine detection of patients at risk of preterm delivery as well as optimise the management and care of neonatal patients in the clinical level. The group hopes that the development of this research line will minimise needless intervention and over-treatment, streamline patient management and achieve the best possible results.

Impact

The main objective of the research centre is to reduce the number of instances of adverse neurodevelopment in children and adults and make a difference in their lives. An important contribution of the team to that extent is the implementation of their research findings into clinical practice through their involvement in the writing of clinical national and international guidelines.

The group is also committed to sharing and spreading their knowledge in maternal-foetal medicine with the general public. They have launched Inatal, the first social website directly related to a medical referral centre. Inatal is aimed to pregnant women with no pathologies but doubts and concerns, and provides objective, useful information about health issues while encouraging the active participation of its users.

In the Cerebra research programme 2008-2013, a multidisciplinary research programme for the evaluation of diagnostic techniques and intervention measures for prenatal brain damage using growth restriction as a model, the Foetal Medicine Research Centre has achieved significant advances in our understanding of brain injury of prenatal origin. They demonstrated that even milder forms of foetal growth restriction are associated with a high risk of neurological damage, improved current understanding and changed clinical management of one of the major cause of neurodevelopmental problems in children. However, as usual in research, discoveries have led to new questions, challenges and ideas for better ways to improve even further towards a real reduction in the number and magnitude of neurodevelopmental problems of foetal origin.

The next six years

Cerebra are delighted to be in a position to provide funding for the Foetal Medicine Research Centre at the University of Barcelona for a further 6 years (between 2014 and 2019) to continue the innovative and influential work in the area of perinatal brain damage.

Big Lottery Fund Boosts Cerebra’s Conference

The Big Lottery Fund has given a grant towards Cerebra’s 2014 annual conference.

Big Lottery Fund logo

Big Lottery Fund logo

Everyone at Cerebra would like to say a huge thank you to the Big Lottery Fund, who have provided a grant of £9,900 towards the charity’s annual conference.

This year’s conference, taking place at the Royal Society of Medicine in London on Tuesday the 7th of October, focuses on ‘Problem solving’: accessing decent services and support for children with complex needs and their families.

This is a one day conference providing academics, practitioners, educators and carers with up to date, evidence-based information on the commonly encountered barriers experienced by disabled children and their families in accessing their legal rights and practical approaches to breaking these barriers down.

You can find out more about this year’s conference, along with previous conferences, by clicking here.

Thanks to this grant we are able to offer a reduced rate for families and students, and extend our early bird offer to the 31st of August. To book your place click here.

The Big Lottery Fund gives out millions of pounds every year to good causes, including community groups and projects that improve health, education and the environment. You can find out more about the Big Lottery Fund on their website.

JLA childhood neurodisability research priorities – Top 10 published!

The James Lind Alliance

The James Lind Alliance

The James Lind Alliance (JLA) research priority setting partnership publishes its top 10 research questions that still need to be answered on the effectiveness of interventions for childhood neurodisability.

The aim of the James Lind Alliance Childhood Disability Research Priority Setting Partnership was to identify and prioritise unanswered questions about the effectiveness of interventions for children and young people with neurodisability from patient, carer and clinical perspectives.

Suggestions were gathered in an open survey, aggregated and framed as research questions, then checked against existing systematic reviews of research evidence to ensure they were unanswered. The topics were initially prioritised in a vote with stakeholders, and then discussed at a workshop by young people, parent carers and clinicians.

The final prioritisation workshop was held on 5 June 2014 at the Royal College of Paediatrics and Child Health in London. Participants in the workshop came from various regions of England.

There were three young adults with neurodisability, seven parent carers, three representatives from generic child disability charities (including Cerebra), a disability advisor in education, and eight health professionals (paediatrician, speech and language therapist, three physiotherapists, occupational therapist, nurse, orthopaedic surgeon). Three representatives from NIHR observed the meeting.

The group succeeded in prioritising the 25 uncertainties shortlisted from earlier stages, and a Top 10 was agreed. The Steering Group will meet again in September to review progress with our dissemination strategy.

To find out more about the work and all the topics considered and prioritised, please visit:

http://www.bacdis.org.uk/research/psp.htm

The Cerebra Centre for Neurodevelopmental Disorders

cerebra-centre-logoIn this article we outline the research being carried out at the Cerebra Centre for Neurodevelopmental Disorders at the University of Birmingham.

Over the last 6 years (2008-2013), Cerebra has provided the core funding for The Cerebra Centre for Neurodevelopmental Disorders, a research centre based at the School of Psychology at the University of Birmingham, headed by Professor Chris Oliver.

The aims of the centre for the first six years of funding (2008-2013) were:

  • to carry out longitudinal, cross syndrome data collection to describe and understand the genetic, physical, neurological, cognitive and behavioural characteristics of children and young adults with genetic disorders associated with neurodevelopmental disorders
  • to conduct exploratory and hypothesis-driven experimental research projects that seek to discover the causes of and effective interventions for behavioural, cognitive and emotional problems in children and young adults with genetic disorders, intellectual disability and autism spectrum disorder
  • to disseminate research findings of relevance to all children and young adults with neurological impairments, intellectual and developmental disabilities who show behavioural, cognitive and emotional problems.
  • To read more about the current and past research projects, please visit the centre’s project pages, or read their annual report on the Cerebra website.  In this video a researcher at the centre explains the impact their research has for children with neurodevelopmental disorders and their families.

    The next 6 years

    Cerebra are delighted to be in a position to provide core funding for the Cerebra Centre for Neurodevelopmental Disorders for a further 6 years (2014-2019). The research taking place will continue to focus on understanding and ameliorating the clinically and socially significant problems that are experienced by children with neurodevelopmental disorders and their families. The centre will focus on three areas of research:

  • refining the behavioural phenotypes of genetic disorders
  • understanding the causes of clinically and socially significant problems experienced by children with neurodevelopmental disorders and their families
  • developing an early intervention strategy to prevent the development of these problems.
  • Understanding and reducing sleep disorders in children with developmental delay

    Cerebra have awarded additional funding to the centre to conduct research that will describe and assess sleep disorders in three groups of children at the highest risk for severe and persistent sleep problems:

  • children with Angelman syndrome
  • children with Smith-Magenis syndrome
  • children with intellectual disability and autism spectrum disorder.
  • The contrasting nature of the sleep disorders will allow the project to:

  • identify critical points for intervention that are disorder-sensitive
  • compare and contrast the effects of different types of sleep disorders on parental wellbeing and physical health
  • develop and trial disorder-sensitive sleep assessment protocols
  • evaluate the effects of behavioural management in proof of principle studies
  • develop cloud and internet resources to facilitate assessment, sleep consultancy, intervention and dissemination.
  • The study of sleep disorders in these three groups affords the opportunity to describe the relationship between different types of sleep disorders in children and their relationship to disturbed sleep, stress, poor physical health and coping in parents. These research findings will be invaluable to inform the Cerebra Sleep Service.

    Further Inform Neurogenetic Disorders (FIND) website development

    Cerebra also co-fund a website project with the Economic and Social Research Council (ESRC), led by the Cerebra Centre for Neurodevelopmental Disorders, that aims to get these research findings about rare genetic syndromes to families and professionals quickly and effectively. The website is named ‘Further Inform Neurogenetic Disorders (FIND)’, and will be launched in September 2014. Keep an eye out for the launch!

    For more information on FIND and the services provided please click on this link to be directed through to the website:  http://www.findresources.co.uk/about-us

    Research update – June 2014

    UpdatepicA selection of recent news, research, reports and events.

    In the news

    Autism resolution passed at WHA Research

    Autism reports that in an immediate board approval, the World Health Assembly (WHA) – the decision making body of the World Health Organisation (WHO) – passed recently a resolution regarding autism, placed by Bangladesh last year. The assembly urged member states to include the needs of individuals affected by autism spectrum and other developmental disorders in policies and programmes related to child and adolescent health and development and mental health.

    Autistic boys exposed to higher levels of hormones in womb, study finds

    The Guardian reports that research on children in Denmark has found that boys with autism were more likely to have been exposed to higher levels of hormones in their mother’s wombs than those who developed normally. The findings add to a growing body of evidence that the biological foundations of autism are laid down well before birth and involve factors that go beyond the child’s genetic make-up. The results may help scientists to unravel some of the underlying causes of autism and explain why boys are four to five times more likely to be diagnosed with the condition, which affects around one percent of the population.

    Research

    Timing is everything: scientists control rapid re-wiring of brain circuits using patterned visual stimulation

    In a recent study published in Science, scientists from Montreal Neurological Institute at McGill University and the McGill University Health Center show for the first time how the brain rewires and fine-tunes its connections differently depending on the relative timing of sensory stimuli. The researchers have been studying the formation of brain circuitry during development to better understand healthy brain wiring. They also hope such studies will lead to development of more effective treatments for nervous system injuries, as well as therapies for neurodevelopmental disorders such as autism and schizophrenia.

    Twin study set to explore autism, attention deficit overlap

    Sfari reports that a new Swedish twin study plans to search for the shared genetic and environmental origins of autism and attention deficit hyperactivity disorder (ADHD), which are often mistaken for each other. The new project aims to assess identical twin pairs using a variety of measures, including behavior and brain imaging. The researchers plan to compare the characteristics of the discordant twin pairs (meaning only one of the two has a disorder) with those of typically developing twin pairs.

    Risk of brain injury is genetic

    Researchers have identified a link between injury to the developing brain and common variation in genes associated with schizophrenia and the metabolism of fat. Scientists at the University of Edinburgh, Imperial College London and King’s College London studied genetic samples and MRI scans of more than 80 premature infants at the time of discharge from hospital. The study builds on previous research, and suggests that premature babies’ risk of brain injury is influenced by their genes, a study suggests. Researchers add that future studies could look at how changes in these genes may bring about this risk of – or resilience – to brain injury.

    Clinical research: Angelman gene variants alter symptoms

    Sfari provide a brief summary of a study published on 19 March in Research in Developmental Disabilities, which reports that the nature of the mutation that leads to Angelman syndrome, a disorder characterized by speech impairment and developmental delays, affects the disorder’s presentation.

    Brain Methylation Map Published

    The Scientist reports on research published on 4 July in Science that shows that epigenetic modification varies greatly over the course of development but is remarkably consistent between individuals and between mice and humans. Researchers at the Salk Institute in San Diego have made an extensive map of several types of methylation in the brains of mice and humans, hoping to understand the role of epigenetic changes in the brain as mental illnesses took hold in humans.

    Reports

    Sensory issues and autism: an insider’s guide

    SEN provides a summary by Paul Isaacs that outlines some of the main sensory difficulties faced by people with autism and how they affect their everyday life.

    Events

    Towards a Positive Future

    A one-day annual national conference for parents of children with special educational needs and the professionals who support them. Central London, Thursday 19th June 2014.

    Engage in their future National Conference

    An exceptional programme of speakers and workshops will be delivered around the theme of ‘Improving life chances for children experiencing behavioural, emotional and/or social difficulties (BESD)’. Wyboston Lakes, Cambridge, Thursday 3rd and Friday 4th July.