Amnesia and the medial temporal lobes: an investigation in autoimmune limbic encephalitis

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The overall aim of this project is to understand how damage to a region of the brain called the medial temporal lobe causes memory impairment. Memory impairment is common in neurological diseases. It can be devastating to peoples' lives, leaving them unable to work and dependent on carers for many daily activities. It has been known for a long time that one particular part of the brain - the medial temporal lobe - is critical for memory. Damage to this region occurs in conditions such as Alzheimer's disease, epilepsy and encephalitis (inflammation of the brain) and may lead to severe memory loss. In order to diagnose and treat these conditions better, we need to understand how the medial temporal lobe is involved in memory.This research project focusses on a neurological condition called limbic encephalitis, in which the medial temporal lobe becomes inflamed. Almost ten years ago, scientists in Oxford identified a common cause of limbic encephalitis - antibodies to the 'voltage-gated potassium channel complex' (or VGKC). This disease, known as VGKC-LE, typically occurs in middle age and is increasingly recognised as a cause of memory impairment and seizures in later life. Treatments are available but many patients have severe ongoing memory difficulties that disrupt their lives. The research will discover what are the causes of memory loss in patients with VGKC-LE and what can be done to prevent them. This will help doctors to recognise the condition earlier and prescribe the best medications. It will also teach us much more about the precise role of the medial temporal lobe in memory.What we learn from this project will be directly relevant to other common conditions such as dementia and epilepsy. It will increase our understanding of why damage to the medial temporal lobes causes memory problems and enable us to detect these problems sooner - a vital step towards finding effective treatments.The research will be carried out by Dr Christopher Butler, a neurologist at the University of Oxford and Oxford University Hospitals NHS Trust. Dr Butler has a specialist interest in memory disorders and runs a multidisciplinary memory clinic where many patients with VGKC-LE are seen. The project will involve one of the world's leading centres for brain scanning - the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB). There is a large group of patients with VGKC-LE in the Oxford region. We will use detailed tests of memory and state-of-the-art brain scanning to discover the causes of memory impairment in VGKC-LE and improve the treatment of this often devastating disease. A special test of memory, developed as part of the project, will be used to try and improve the early detection of Alzheimer's disease.