What’s Happening in Cerebral Palsy Research Around the World?

Click here to download the report.

Research into cerebral palsy has a history dating back to the 1840s when William Little first sought to understand the condition. There is an active, global research community that has undertaken some high-quality work that has advanced our understanding of CP. However, there’s a lack of a central resource for those with a professional interest or have been directly affected by CP that defines and describes the vital research that has been and is being undertaken globally, so we have commissioned a review of what research was either underway or had recently reported.

The review, Cerebral palsy: causes and prevention by Dr AnnieBelle Sassine, highlights 150 research studies that have added significantly to our knowledge and has also helped us identify the gaps in research activity based on what we now understand about CP and understanding the state of research funding.

While the picture is limited to what we were able to discover through publicly available sources, our review also provides enough of a picture to raise some concerns for anyone with an interest in combatting CP.

Much of this concern centres on the commonly-held view of CP as a comparatively ‘rare’ condition, meaning that research investment is significantly less than for conditions with higher incidence and prevalence. While CP’s incidence is estimated to afflict between 1.5 and 4 babies in every 1,000, no one knows this for certain as there are no universally consistent means of diagnosing CP or reporting its incidence in either the developed or developing worlds.

This ‘rarity’ argument also ignores the disproportionate social cost that is CP’s legacy: the condition is lifelong and frequently involves 24-hour care for those affected. National social-/health-care budgets and those of medical insurance companies for those not supported by a national health service continue to be stretched by the need for ever-increasing provision: CP costs the UK alone well over £1.6 billion every year. Yet the amount invested annually on research by government and other charities is worryingly small: the figure for the UK is less than £5 million, 0.23% of research funding. The UK is not alone in this – our report also reveals a similar picture of cost : investment disparity globally.

We have compiled summaries of the key research studies identified in Cerebral Palsy: causes and prevention to help explain their impact on our understanding of CP. Click here to access a database of the summaries.

Cerebral Palsy Research Database

We regularly survey the global research community’s effort to combat cerebral palsy and have identified over 7,000 research projects worldwide which demonstrate the span of approaches to CP by the world’s research community. We have brought all these together for the first time, creating a searchable database available to everyone. Available to search below (i.e. ‘epidemiology’, ‘Cochrane Review’ etc.):

What’s the Future of Cerebral Palsy Research?

Our report draws some potentially significant conclusions that will shape our own research strategy and policy but which will also help inform new directions for research into cerebral palsy in the UK and, eventually, globally.

We feel it is important that the research community focuses its attention and resources on these key areas:

Strategies that reduce the incidence of preterm birth are likely have a positive effect on reducing the incidence of CP. Research to identify pregnancies at higher risk of being pre-term is important, taking into account maternal risk factors, obstetric history, foetal screening and predictive biomarkers.

Key priorities for future research involve maximising the use of existing datasets to build further evidence on the specific factors that increase risk of CP. New population studies are required to gather more comprehensive information about how genetic, lifestyle and environmental factors contribute to CP and other neurodevelopmental disorders. We also need to develop randomised controlled trials to test existing interventions for conditions such as stroke, haemorrhage, thrombosis or infection, for their effect on reducing the risk of these threats to babies during pregnancy.

Infections during pregnancy such as toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus have been associated with increased risks of CP. A better understanding of the types of infection that contribute to pre-term delivery is also needed. When we’re able to point to evidence of viral infection, we can develop strategies and action for prevention.

Evidence indicates a correlation between maternal nutritional factors (particularly omega-3 fatty acids) and healthier neurodevelopment in children. Further research is required to identify effects that are directly linked to CP and define the mechanisms of action. These would need large population studies recruiting at least 50,000 pregnancies, collecting data and tissue samples.

Prof Michael Crawford and Prof Mark Johnson’s work in this area has already produced substantial insights – here he talks about what we’ve learned so far and where research needs to go now.

Whilst neuromotor abnormalities can be the result of an insufficient supply of the thyroid hormone in pregnant mothers, more evidence is required to understand if thyroid hormone deficiency has a role in causing CP.

Some studies have suggested an increased risk of CP with gestational diabetes in some people, but without any proof. New and robust scientific studies are needed to test this possible association.

Further research is needed to determine the genetic susceptibility of babies to developing CP and other neurodevelopmental conditions. While environmental factors are likely to be the major contributors to causing CP, evidence suggests that genetics may possibly play a role: for instance, it’s possible that genetic factors may make a foetus more susceptible to brain injury triggered by certain environmental factors. Further study will need to assess the contribution that genetic factors make to specific subtypes of CP, while we also need to improve our understanding of the links between genetics and preterm birth.

Research is required to predict individual risk of CP, based on analysis of the contributing environmental and genetic factors. Through such stratification, we can understand who is vulnerable to brain injury, why some are more vulnerable than others and which factors contribute to specific sub types of CP. Individuals identified as being at high risk can receive evidence-based interventions alongside increased foetal monitoring. Stratification of CP is also important for providing a precise, individual diagnosis and informing the best course of therapy.

We need a much better understanding of how the normal brain develops to understand better what goes wrong in CP. We need a better understanding of the brain systems that control motor function i.e. muscles, movement and coordination, which will help us to link injuries in specific areas of the brain to specific motor problems. It can also help us to define when the baby’s brain is more susceptible to injury, identifying the origins of CP and when it might be possible to intervene. The timing of the brain lesions is still not fully elucidated and although many studies show that the aetiology of CP has its origins in the prenatal period, it is important to identify specific time periods after which cerebral damage might become irreversible. This will be crucial for all preventive interventions.

Damage is thought to occur in the white matter of the brain, involving a cell type called oligodendrocytes. Engaging neuroscientists in the study of oligodendrocytes and glial cells and their clinical application in CP is important.

We also need to understand which cell types and biological pathways must be targeted in the brain to prevent the onset of CP, promote repair to injury or stimulate neuroplasticity. Further research is required to determine whether direct targeting of oligodendrocytes is beneficial or whether other cell types in the neuronal microenvironment should be targeted.

Animal models are an important tool for the study of brain development and injury. In addition, the use of MRI and non-invasive imaging provide powerful tools for understanding brain development in humans.

We need a better understanding of the actual mechanisms that occur in the brain that lead to injury, and why foetuses respond to injury in different ways. Further research is required to identify the key cascade of biological events that occur in response to a trigger event and how these can lead to brain damage. More sensitive approaches are required to detect and monitor neonatal seizures.

The incidence of, and mortality from, CP is particularly high in low income countries (LIC). More research is required to understand the factors that contribute to the high incidence of CP in these countries.

The early detection and treatment of Hypoxic Ischaemic Encephalopathy (HIE), whilst not preventing brain injury would have the potential to reverse the damage, thereby preventing the development of CP. Once we’ve been able to detect HIE early on, we need to explore using different, existing treatments, for example by applying knowledge on treatment for stroke, haemorrhage, thrombosis and inflammation.

Research to deliver therapeutic benefits from stem cells has a long way to go, with claims of their therapeutic potential currently being overstated. However, we do need to explore the potential for stem cells from the mother can provide neural protection or repair therapy for babies.

While clinicians can indicate in some cases early on that it’s likely, CP is undiagnosed until babies are aged 18-24 months when it is more apparent. However, the scope for improved recovery and rehabilitation from brain injury could be considerably greater if we were able to make an accurate diagnosis much sooner.

Recent studies suggest that an accurate diagnosis could be made at six months, based on a review of mothers’ medical histories, neuroimaging and standardised neurological and motor assessments. While these findings have led to the development of new guidelines for the earlier diagnosis of CP and contributed to changing clinical practice, further research is required to better understand which factors, such as the patterns of brain injury at birth, are better predictors of whether a child will have CP.

We also need more research to identify, develop and validate biomarkers for early diagnosis (by combining data from foetal imaging, genetics, and early movement assessments), which would significantly improve clinical outcomes.

Due to the complexity associated with pregnancy and childbirth, instances of CP will, sadly, be inevitable for a long time to come. Nevertheless, with greater investment in research there is substantial scope to dramatically reduce the incidence and societal impact of CP, and to explore better approaches to treat, rehabilitate and lessen its effects.

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