SCT Encephalitis lethargica surveillance and research programme: update
David Holden & Gavin Giovannoni

This report covers the first year of the surveillance and research programme, from September 2007 to September 2008 inclusive.

1. The paediatric surveillance programme commenced in December 2007, and is being conducted through BPNSU. The adult surveillance programme was delayed pending resolution of a query sent by BNSU, but commenced in April 2008.

2. The EL database is being maintained at QMUL, stored on a secure QMUL University server, which is backed-up on a daily basis. Following a meeting with Dr Joel Vilensky in June 2008, database design is based on a data collection pro-forma originally designed for Dr Vilensky’s historical study. This will allow comparison of comparison of current surveillance data and historical data, and allow results to be available online (DH).

3. Mr David Holden and Professor Gavin Giovannoni attended a symposium on the Role of Autoimmunity in Tourette’s Syndrome and Related Disorders, as part of the Italian Movement Disorders National Congress, in Bari April 4-5 2008. David Holden presented a poster entitled “Encephalitis lethargica: surveillance and immunological studies”. This described the EL surveillance programme, and related investigations into the immunological basis of this disease, both of which are supported by funding from the Sophie Cameron Trust. The presentation of an EL poster at this meeting had the effect of raising awareness of the disease, and placing it in the context of related neuropsychiatric disorders. A flyer describing the surveillance project was distributed at the meeting.

4. As of October 2008, 15 paediatric EL cases have been notified through the BPNSU scheme and confirmed through the surveillance programme – a feature of both the BPNSU and BNSU schemes is that a number of erroneous cases are initially reported. Four adult EL cases have been notified via the BNSU scheme, one of which has been confirmed to date. The current notification rate is approaching the expected 20 cases per year; however, this is likely to include a backlog of cases from 2007 and previous years. A letter of support from the Sophie Cameron Trust has been included with the information sent to patients identified by the programme.

5. Professor Gavin Giovannoni has registered the domain name www.encephalitislethargica.org to create a website for the SCT EL surveillance and research programme. We plan to create a wiki using this domain to allow user-generated material to be posted on the site. We plan to go live with the wiki in 2009.

6. The SCT EL Surveillance Programme will generate added value if it is continued indefinitely and if the surveillance programme is widened to receive cases from outside the UK.

7. The Neuroimmunology Unit at ICMS-QMUL are conducting a research programme to investigate the functional significance of ABGA. This project is supported by the SCT. Further investigations are likely to require further biological samples, which will be obtained via the EL surveillance programme. Attached is a report by Joseph Cohen, an intercalated MBBCh-BSc student, who did his laboratory project on this aspect of the research. Joseph results were very interesting and he was sufficiently motivated to return for an 8 week period over his summer holidays to continue the work and study additional cases.

8. In collaboration with Dr Jenny Pocock we have also taken on Kathrin Hoffman, a German MSc student, for a further 8 months to expand on Joseph’s work. Her research work is being sponsored by the SCT grant.

9. We have also appointed Ms Priya Dua to the SCT PhD Studentship for a period of 3 years. During this time Priya will be trying to set-up an animal model of encephalitis lethargic based on the streptococcal hypothesis.

4th November 2008

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SEMINAR BY PROFESSOR VILENSKY

On 17th June 2008, Richard Steele and Richard Wharton, on behalf of the Sophie Cameron Trust, visited the Institute of Neurology in Queens Square, London. We had invited Professor Joel Vilensky of Indiana State University, USA to London to speak at the institute on encephalitis lethargica (EL). Prof. Vilensky has developed an encyclopaedic knowledge of the history and current state of the disease, and has unique access to records, documents and film footage from the epidemic in the 1920s. This has extended well beyond the USA, and he is in contact with researchers in Russia, Israel, South America, and elsewhere. He has documented the many recorded types of presentation of EL, and is developing a database which relates these to cases in a way which should help us understand the disease better. He has started work to write a definitive reference work on EL which will be published by Oxford University Press, hopefully in 2010. This work will be dedicated to Sophie, with a foreword by Richard Steele, and chapters will be contributed by many workers in this field including Professor Giovannoni, our scientific adviser. Research for the book is funded by SCT.

 The lecture, at the Wolfson Lecture Theatre, National Hospital for Neurology and Neurosurgery, Queen Square, London, was attended by about 80 people including a number of eminent neurologists. It was co-chaired by Professors Andrew Lees and Roger Lemon. Prof. Lees is a co-author of an important paper on EL in the 1980s. Prof. Vilensky covered a huge amount in an hour, expounding the history, showing film of cases, and summarising the present position of cases and research. Particular aspects of EL which are almost unique include “false sleep”, where the patient appears to be asleep but is fully aware of and can remember events around them; and catatonia where they appear motionless for long periods, but can accurately catch a ball and throw it back. Cases in the 1920s included the centre forward of the national Hungarian football team, who later became catatonic. Another fascinating insight was the history of the disease in Samoa in the Pacific. During the worldwide flu epidemic, a ship from New Zealand docked in Western Samoa and flu spread through the islands, along with documented cases of EL. Meanwhile American Samoa nearby prevented the arrival of flu, and had no cases of EL at all. Researchers including Professor Oxford, who was in the audience, have tried for years to establish a link between the flu virus and EL, but have been unable to do so. Some of the discussion after the talk was quite technical, but Dr Gerald Stern, Emeritus Professor of Neurology, recalled the cases at Highland Hospital in north London which he had supervised and discussed with Oliver Sacks in the 1970s, and some of their bizarre behaviour.

All in all the talk was judged a great success, and SCT look forward to cooperating further with Prof. Vilensky in the future. Afterwards, he met with our team of Prof Giovannoni, Dr Annette Schrag, and David Holden, our research coordinator. The National Surveillance programme in the UK has started in March, and so far 15 cases of EL have been notified. This figure may be high, as neurologists may be recalling recent cases from the last few years, but we expect there to be a trickle of new cases as well. Where consent is obtained from patients, details can be logged using the database developed by Prof Vilensky in the USA. Each case will be sent details of the Sophie Cameron Trust. There is also growing evidence of cases all around the world, including 8 cases in Miami, Florida; a group in Israel; and new evidence from Thailand. Both professors have also been in touch with neurologists around the world about individual cases, especially in South America, and Dr Russell Dale, who co-wrote a paper we sponsored 3 years ago, is now based in Sydney. So we can see a worldwide research net into this rare disease developing.

Dr Andrew Church at ION still provides a test for antibodies to the basal ganglia in the brain, where movement is co-ordinated, and these antibodies are found in many cases of EL. Our next major research project is a three-year Ph. D. studentship to study these antibodies, known as ABGAs for short. Gavin Giovannoni will oversee this, and after interviewing a number of candidates, has appointed Ms Priyamvada Dua from Delhi, India. Ms Dua, who has taken an M.Sc. at Imperial College, London, will commence work in September. Gavin described her as an outstanding candidate, and hopes to arrange for us to meet her in the autumn. We will be covering her basic salary and some of the research costs for three years. Finally, we discussed how this explosion of research can best be coordinated and disseminated worldwide. It was suggested that the SCT website have a sister site designed for clinicians and maintained by the team in London, but with close links to SCT. We will be pursuing this idea in the coming months. Overall, it is astonishing how much the trust has achieved in the last few years, and we anticipate the next few years will be equally exciting. Many thanks to all our supporters and tireless workers who have made this possible.

Richard Wharton and Richard Steele June 2008