Supervisors: Dr Jemma Day, Dr Grainne McAlonan and Dr Jonathan Muircheartaig, Prof Anil Dhawan
Covert hepatic encephalopathy (CHE), a spectrum of neuropsychological problems of patients with chronic liver disease (CLD), is caused by an accumulation of toxic substances that are normally removed by the liver. We know this affects up to 80% of adults with CLD, with validated methods of identification, monitoring and treatment available. However, as yet, the impact of CLD and CHE on the developing brain of infants and children is unknown. The quality of life of young people growing up with CLD is considerably less than their healthy peers, with significantly fewer attending third level education or maintaining employment. Although a neurodevelopmental disability is not currently a recognised part of CLD in children, we hypothesis that subtle CHE may contribute significantly to cognitive / developmental impairment. Timely detection and management may result in reversal of this effect, and improve long-term quality of life.
The pathophysiology of CHE is multifactorial, with an overproduction of toxins such as ammonia in the bloodstream and brain, leading to cell swelling and low-grade cerebral oedema. Longitudinal neuroimaging research has demonstrated that the brain goes through considerable change and development during the first 3 decades of life (Giedd et al., 2008). It is currently unclear how chronic exposure to these toxic substances affects the developing brain, and whether there is an insidious impact upon development and cognitive functioning in children with CLD.
Indeed, preliminary data suggest that children with CLD are at risk of developing a cognitive impairment (Stewart et al., 1992) and developmental lag (Caudle et al 2010: 2012; Robertson 2013). Data consistently demonstrate poorer educational attainment in children with CLD (e.g. Kaller et al., 2012), which appears to be over and above those of children with other chronic illnesses and comparable school absence due to hospitalisation. It is reasonable to assume that this could be attributable, at least in part, to undetected CHE, yet this mechanism remains unexplored. Only when these effects are understood will we be able to employ strategies to mitigate the consequences of CHE on long-term cognitive development, for example, medical treatments used in adult with CHE, or considering earlier liver transplantation.
We are pleased to offer a PhD opportunity to join our team and work with infants, young children and their families to examine the impact of CHE on the developing brain. The project will use validated repeat (4-6 months) assessments of development and cognition to determine the potential longitudinal impact of CLD. There will be the opportunity to include imaging data (MRI & spectroscopy) to gain insight into the impact of CHE on the microstructure of the brain in these children. Imaging infants diagnosed with liver disease soon after birth, and following them up longitudinally, will allow us to test whether earlier age at transplant impacts on the developmental trajectory of both brain growth and cognitive development. This innovative multidisciplinary project provides unmatched breadth and depth of skills training and has the potential to rapidly impact upon our understanding and treatment of CHE in infants and children with liver disease.
The proposed project would involve close collaboration between King’s Health Partners, including the following CAGS: Child Health Clinical Academic Group, Clinical Neurosciences Clinical Academic Group, Behavioural and Developmental Psychiatry, Clinical Academic Group, Imaging and Biomedical Engineering Clinical Academic Group) to implement this joint research.
King's Paediatric Liver Centre is a national hub providing a highly specialised service to children with liver problems. Children are assessed and treated for neonatal liver diseases, chronic (long-standing) liver disease and acute liver failure. The MowatLabs have been developed primarily for research into children’s liver disease and acute liver failure, in close collaboration with the adult liver unit at the hospital. The £1.2m state-of-the-art laboratories – which have been funded entirely through philanthropic donations – bring together clinicians, researchers, nurses, intensivists, surgeons and transplant specialists, in a collaborative research environment. King’s College Hospital has the only joint paediatric and adult liver facility in the world. It is home to the world’s largest children’s liver unit, treating over 3,000 young patients a year, and is at the forefront of pioneering new treatments.
The Institute of Psychiatry, Psychology and Neuroscience at King's, the largest academic psychiatric community in Europe links with South London and Maudsley NHS Foundation Trust to access approximately 30,000 outpatients. Thus, working here provides exposure to a unique resource of basic science and clinical expertise for the student. The Centre for Neuroimaging Sciences is equipped with state of the art imaging facilities, including two GE 3T MRI clinical research scanners and support from a dedicated team of engineers, physicists, statisticians, radiologists, and image analysts.
The student will have comprehensive training, including in the acquisition and analysis of paediatric data, the psychological assessment of patients with liver disease, data computation and analysis, as well as specific training in clinical ethics, recruitment and assessment. Training in the analysis of MRI spectroscopy data will be provided as needed.
Applicants should have (or be expected to obtain) a 2:1 or 1st class honours degree in a subject relevant to the proposed project. If applicants already possess (or expect to obtain) a research-based MSc degree, a merit or distinction level is required.
This project would be particularly suitable for candidates with an interest in developmental psychology, neuropsychology and neurodevelopment.
How to Apply
Applicants must complete and submit an online admissions application, via the admissions portal by midnight (12:00 GMT), 31st December 2018.
On the ‘Choosing a programme’ page, please select ‘Research degrees’ and enter the keyword JDEnceph2018. Further information can be found https://www.kcl.ac.uk/study/postgraduate/apply/research-courses.aspx
In your application, you will be asked to include:
• Academic Transcripts – where applicable, academic transcripts must be submitted with the online admissions application
• Details of your qualifications (you will need to attach copies)
• Details of previous employment
• A personal statement describing your interests and why you wish to apply for this project. Please include this as an attachment rather than using the text box.
• Academic References – all admissions applications require two supporting references. If the applicant is relying on his/her referees to submit references directly to the College after he/she has submitted his/her admissions application, then the applicant must ensure that their chosen referees are made aware of the funding deadline.
Please note there is no need to complete the Research Proposal section in your application as the project has already been set. You are welcome to email Jemma Day (supervisor) for more information regarding the project and studentship, details above.
If you have any queries regarding the application process, please contact the Postgraduate Research Administrator.
References must be received by the deadline for the applicant to be eligible.
Only shortlisted applicants will be contacted.