Understanding and improving the outcome of viral encephalitis

Aims? To determine the clinical predictors of viral encephalitis, and poor outcome ? To better understand those outcomes in terms of cognitive function, quality of life, and cost? To develop the means of intervening to improve the outcomeBackgroundViral encephalitis (inflammation of the brain substance) is one of the most important types of brain infection because of its devastating impact on those affected. It has a disproportionately large burden on the NHS and community through high health and economic costs, but this has never been quantified. In terms of research, viral encephalitis is relatively neglected, because it is not easily funded from other sources, e.g. major charities.Patients with encephalitis have difficulties at all stages of the patient journey, including:? Difficulty in accessing appropriate health care when they become unwell, because of the non-specific nature of their early symptoms? Shortcomings in the initial management, so that there are delays in investigation and treatment? Poor understanding about the neuropsychological and social sequelae, and effects on carers, so that long term planning is difficultHerpes simplex virus (HSV) is the most common cause, and is treatable with aciclovir, but delays in treatment are associated with poor outcome. There has been little research into how and why delays occur. There are no health economic data from the UK, but typical medical negligence settlements of £1-2 million for a single encephalitis case where the management was negligent give some indication of the overall costs to society. The proposed research programme builds on pilot data from previous work by the Liverpool Brain Infections Group, the Encephalitis Society, and preliminary findings from the HPA Cohort studyResearch Plans (SEE APPENDIX 1 & 2 Programme Overview, and Gantt chart).? Establishing a new prospective multi-centre cohort of patients with encephalitis across the UK (for brevity, referred to as the Enceph-UK cohort study)? Capitalising on a patient cohort established through the Department of Health (DH)-funded Health Protection Agency (HPA) study on the Aetiologies of Encephalitis (the HPA cohort study)? Developing an intervention based around Management Guidelines, and examining its role through a cluster randomised trial.Studies1. Determination of the clinical features predictive of viral encephalitis, and of outcome, with a prospective cohort study.2. Examining experiences of end users in relation to acute management (from the Enceph-UK study) and long term care (from the HPA cohort).3. Investigating the effects of encephalitis on quality of life4. Determining the total costs of viral encephalitis.5. Evaluating the role of combined neuropsychological testing and quantitative magnetic resonance imaging in predicting clinical, cognitive, and psychiatric outcomes 6. Development and evaluation of an intervention based around the National Guidelines on the Management of Suspected Viral Encephalitis, with a Cost Analysis.The interrelated nature of the 6 studies, using the three “patient groups” (HPA Cohort, Enceph-UK cohort, and the Cluster Trial) to achieve the aims gives added value to the programme.Research TeamThis comprises international experts with considerable experience in all the necessary disciplines (brain infections, clinical trials, neuropsychology, imaging, health economics, qualitative research, psychological and social studies, statistics). Many of the team have worked together before, but bringing them all together on this single programme will provide added benefit developing a strong team for future research in this important area.Research EnvironmentProgramme hosted by the Walton Centre / University of Liverpool Brain Infections Group, where Neuroscience, and Infections are major themes. Liverpool already holds two NIHR Programme Grants in Applied Research.Anticipated Outputs and Outcomes? Information about the outcome of encephalitis (health, neuropsychological, ec