What is encephalitis lethargica?
Anette Schrag & Gavin Giovannoni
Encephalitis lethargica (EL) or von Economo’s disease is an acute, usually severe illness, with inflammation of the brain. It can be associated with fever, headache, lethargy, and psychiatric and neurological features in the acute phase, including coma in some cases. It may leave patients with long-term neurological and psychiatric consequences. The disease was first recognised in the in the early 1900s when an outbreak affected large numbers of people worldwide. Whilst it was initially thought to be related to the 1918 influenza pandemic, recent evidence makes this unlikely as a direct cause. At present it is a relatively rare disorder but it still occurs sporadically. At present we don’t have accurate figures on how common it is.
Presentation: Whilst the exact frequency or incidence, presentation, disease course, treatment response and disease mechanisms are relatively undefined, there are some classic or typical presentations: EL often presents as an acute illness in young adults (and sometimes children) with initial fever, headache, lethargy, visual symptoms, muscle weakness, neuropsychiatric features (e.g. confusion, hallucinations, behavioural changes), altered consciousness state (e.g. drowsiness) and sleep disorder (increased or decreased sleep). In addition, many patients develop a movement disorder, with either parkinsonism (reduction in movement) or abnormal increase in movements of various kinds, affecting limbs, trunk, face or eyes. This may sometimes develop many months after the onset of the initial illness. Typically behavioural and motor disturbances fluctuate over hours or days. Laboratory tests may show abnormalities of the cerebrospinal fluid (CSF - the fluid that the brain and spinal cord float in), abnormalities of brain imaging and negative tests for other known infectious and inflammatory cerebral disorders.
EL may be fatal or result in severe neurological consequences. Treatment is mainly aimed at improving the symptoms produce by the disorder, e.g. with medications for the movement disorder or the psychiatric symptoms. No specific treatment for the underlying disorder is available at present.
The exact cause of this disorder is still unknown. However, studies on the brain, cerebrospinal fluid and blood of patients with EL suggest that the disorder is autoimmune in origin. This means that the patients own immune system goes awry and attacks certain areas of the brain. Research is being undertaken to address the “autoimmune hypothesis” and determine if this disorder is caused by antibodies directed towards the brain. It is important to realise that certain viral infections of the brain, for example Japanese B Encephalitis, which is common in Asia, cause a disease that can look very similar to EL. Because of this, it is quite possible that EL has more than one cause.
The Sophie Cameron Trust is therefore supporting research to address these unresolved issues to determine the exact frequency, presentation, disease course, treatment response and underlying disease mechanisms. The aims of this study are to
- Learn how frequently EL occurs and what range of symptoms it can present with.
- Learn whether this disorder is related to antibodies directed towards the brain.
- Store patient samples for future use when new tests become available and new possible causes are discovered.
This study will collect information from patients with EL from the whole of the UK and will last for 10 years. This will allow the collection of more information on this relatively rare disorder than individual centres can provide.
All patients with possible EL identified by their neurologists or paediatrician, will be asked to take part in the study. The hospital records of those who agree to participate will be examined and they may be contacted and be invited to donate any leftover blood from a blood sample, portion of CSF or other specimens from routine examinations. These samples will be tested for specific immunological markers, such as antibodies to certain parts of the brain, which would not be routinely tested for in clinical practice, and a portion of each sample will be stored for future use, if and when further tests become available. Participants will also be asked a number of questions on their symptoms and health.
The results of this study will be made available through the Sophie Cameron Trust and through research publications.
Dr Anette Schrag, MD, PhD
Senior Lecturer and Honorary Consultant Neurologist
University Department of Clinical Neurosciences
Royal Free and University College Medical School
Rowland Hill Street, London NW3 2PF
Professor Gavin Giovannoni MBBCh, PhD, FCP (S.A., Neurol.), FRCP, FRCPath
Professor of Neurology and Honorary Consultant Neurologist
Institute of Cell and Molecular Science, Queen Mary University London
Department of Neurology, Barts and The London NHS Trust
The Royal London Hospital
London E1 1BB
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