On December 3rd, 2018, over 100 healthcare professionals congregated in London for the Encephalitis Society’s 2018 conference. This was my first attendance, and with delegates from over 13 countries it was clear this was an international affair, attracting exceptional researchers, scientists, clinicians and professions allied to medicine. Throughout the day the packed house were captivated with a series of speakers representing a wide-range of disciplines including neurology, neuropsychology, neuroscience, sociology, and psychiatry.
Chaired by Professor Tom Solomon, the opening address entitled “Anti-NMDAR encephalitis: symptoms, mechanisms and disease models” was presented by keynote speaker Professor Josep Dalmau. Professor Dalmau began by discussing the relationship between structural brain changes and neuropsychological outcomes. The hippocampi appear to play an important role in anti-NMDAR encephalitis with hippocampal connectivity correlating with memory and hippocampal atrophy correlating with disease duration and severity. Professor Dalmau then presented findings of a recent study suggesting that herpes simplex virus encephalitis (HSVE) can precede autoimmune encephalitis which leads to neurological worsening. In this prospective study 27% of patients with HSVE developed autoimmune encephalitis and all presented with new neuronal antibodies. A large proportion of these antibodies (64%) were shown to be targeting the NMDA receptor suggesting a specific mechanism by which HSVE can lead to anti-NMDAR encephalitis. Professor Dalmau concluded his presentation by discussing how the field of immunology will play an important role in developing an active model of immunisation and the role of neuroscience in elucidating the role of NMDA brain networks.
Following the keynote address, Dr Adam Al-Diwani presented his work demonstrating the role of psychiatry in the early stages of anti-NMDAR encephalitis. Patients with anti-NMDAR encephalitis often present with psychiatric symptomology leading to frequent misdiagnosis resulting in delayed treatment. Dr Al-Diwani’s research focuses on identifying the characteristic psychiatric features of antiNMDAR encephalitis. Indeed, if potential antiNMDAR encephalitis can be identified based on characteristic psychiatric symptomology time to correct diagnoses can be reduced and clinical outcomes improved.
Ms Raia Blum from the Department of Neurology at the Icahn School of Medicine in New York presented her work on the psychosocial outcomes of autoimmune and infectious encephalitis. Ms Blum reported persistent neurological symptoms and worsened psychosocial functioning in patients with autoimmune and infectious encephalitis. Importantly, this research highlights specific areas of psychosocial functioning that are affected by encephalitis which could lead to targeted, long-term psychosocial interventions to support individuals with encephalitis in the community.
Ms Amanda Tomlinson, a medical student from the Icahn School of Medicine, presented research on the transition of patients with autoimmune and infectious encephalitis and its impact on caregivers. Specifically, Ms Tomlinson reported that caregivers are dissatisfied in the transition from inpatient to outpatient care and experience high levels of caregiver strain. Ms Tomlinson concluded the presentation with a call for more research on these important aspects of patient care.
After a short break, Dr Bonnie-Kate Dewar chaired the second morning session and introduced the first speaker Dr Sylviane Defres. Dr Defres engaged the audience with preliminary data from the ENCEPH-UK project, a large, multicentre programme aimed to understand and improve outcomes for patients affected by encephalitis. Prompt diagnosis and treatment administration is important for disease outcome in encephalitis. The findings from the ENCEPH-UK study showed differences between different types of encephalitis in relation to hospital admission and commencing treatment and differences in the outcomes.
Ms Julia Griem also presented outcomes from the ENCEPH-UK study on neuropsychological outcomes. Despite significant advancements in the treatment and management of different forms of encephalitis patients are almost always left with neuropsychological deficits. Of further note was the discrepancy between objective measures and subjective reports, especially at >1 year post-illness: objective tests showed overall little neuropsychological impairment but patients reported high subjective complaints. Ms Griem provided a succinct summary of the neuropsychological sequelae associated with encephalitis showing that memory impairments correlate with medial temporal lobe damage.
Asst Professor Michael Wilson presented “Clinical metagenomic next-generation sequencing (MNGS) for diagnosis of infectious meningitis and encephalitis.” Professor Wilson’s presentation focused on demonstrating the efficacy of MNGS in identifying the aetiology of meningitis and encephalitis. Numerous viruses, autoantibodies, bacteria, fungi and parasites have been identified and shown to cause encephalitis. However, in approximately half of cases no cause can be identified. The novel application of MNGS in relation to encephalitis and meningitis could help identify infectious aetiologies in idiopathic cases. Professor Wilson illustrated this via a case study of Hepatitis E Virus (HEV) associated meningoencephalitis in a lung transplant recipient, diagnosed through clinical metagenomic sequencing.
To conclude the morning session Dr Lance Turtle presented his research on the diagnosis of acute encephalitis syndrome in South India. Dr Turtle described the challenges inherent in obtaining a microbiologic diagnosis whilst conducting research in Bellary and Bangalore, which included several logistic and clinical issues in processing samples for diagnostic testing. Unfortunately, such problems are common in South India resulting in many patients not receiving a specific diagnosis.
Following lunch, Dr Nick Davies chaired the first afternoon session and introduced Dr Susan Hills from the United States Centers for Disease Control and Prevention (CDC). This keynote presentation focused on the changing epidemiology of arboviral encephalitis. Dr Hills presented data gathered at the CDC showing the number of vector borne diseases in the US has tripled in the period from 2004 through 2016. This corroborates international research demonstrating a rapid emergence of arbovirus diseases globally. Dr Hills also presented information on arboviruses long recognised as causing encephalitis but with changing epidemiology, including West Nile virus, Powassan virus, and Japanese encephalitis virus. Finally Dr Hills described several arboviruses that have emerged in recent years which are not primarily arboviruses causing encephalitis but which can present with neurologic presentations, including chikungunya virus and Zika virus. She noted that new non-vector-borne mediums of transmission for Zika virus have been recognised since 2015 such as sexual transmission and intrauterine transmission, and possibly transmission through blood transfusion and breast milk.
Following the keynote address, Dr Ava Easton, Chief Executive of the Encephalitis Society presented three cases of Japanese encephalitis in returned UK travellers. This thought-provoking talk was a welcome reminder why many of us attending the conference are dedicated to preventing encephalitis and improving outcomes for patients. The three individuals presented all received significant support from the Encephalitis Society and this talk provided a sobering reflection on the remarkable work conducted by the Society.
Dr JM de Vries presented “Mimics of autoimmune encephalitis – a retrospective cohort study”. The diagnostic criteria for autoimmune encephalitis (AE) is heavily reliant on antibody testing, and immunotherapy response which might impede a prompt diagnosis. Recent research has focused on improving provisional diagnosis to improve immediate treatment options which has resulted in the development of a ‘probable AE’ category. In the recently published criteria for AE (Graus et al, 2016) also a novel diagnosis of ‘probable seronegative AIE’ is included, a diagnosis by exclusion based on strict criteria. Dr de Vries showed that within the group of presumed seronegative AE, mimics are important to consider as treatment and prognosis differ. As none of the 40 AE mimics fulfilled the Graus criteria for probable seronegative AE, these criteria seem valid. Among the AE mimics, the most frequent diagnosis were central nervous system (CNS) inflammatory disorders and CNS infections. Disconcerting were the CNS malignancies mimicking AE. In 7 AE mimic patients a cerebral biopsy was indicated to make a final diagnosis, in four of them revealing a neuro-oncologic diagnosis, in two primary CNS vasculitis and in one Whipple’s disease. It is important that clinicians consider AE mimics to ensure effective provisional treatment.
Dr Frederik Bartels presented “Clinical and MRI outcome predictors in paediatric antiNMDA receptor encephalitis”. First, Dr Bartels corroborates much of the neuroimaging research present throughout the day through showing that anti-NMDA receptor encephalitis is associated with significant structural and functional deficits. Dr Bartel’s research demonstrates that brain volume at onset has strong predictive value of disease outcomes. For example, brain volume at onset predicts disease severity and disease course, and an abnormal MRI at onset and brain volume loss predict disease outcome.
Asst Professor Arun Venkatesan chaired the final session of the day commencing with Dr Fabiane Docagne, who presented a novel mouse model of anti-NMDAR encephalitis. Dr Docagne demonstrated that this new mouse model can reproduce the typical signs of antiNMDAR in humans and that it is driven by B-cell mediated autoimmune responses.
Dr Melanie Ramberger, Oxford Autoimmune Neurology Group, presented her research on “Antigen-specific B- and T-cell interactions in patients with LGI1- antibody encephalitis”. LgI1 (leucine-rich glioma inactivated 1) encephalitis has only recently been described and occurs when antibodies attack the LgI1 receptor. Melanie’s research demonstrates that HLA antigen-specific T-cells interact with circulating B-cells, producing antibodies that target the LgI1 receptors. Describing the disease mechanisms provides potential therapeutic targets.
Phillippa Chapman of the Encephalitis Society presented their plans for the coming year. Of important note is World Encephalitis Day on February 22nd, a global awareness day organised by the Society. Further, 2019 marks their 25th anniversary which will be celebrated with a range of events and activities throughout the year as well as the launch of a new PhD fellowship and inaugural research seed-funding meaning that researchers around the world can apply for up to £10,000 per project.
Excellence in Encephalitis Healthcare awards were awarded to Dr Sylviane Defres and Hayley Hardwick, both from the Institute of Infection and Global Health, University of Liverpool. The awards recognised their work on the EncephUK study.
Best Oral presentations were awarded to Raia Blum and Amanda Tomlinson, whilst best poster presentation was awarded to Dr James Varley, Oxford Autoimmune Neurology Group, and Dr Vera Forminykh, Bujanov Moscow City Clinical Hospital.
Closing remarks were delivered by Professor Tom Solomon, and this was followed by a networking opportunity over cheese and wine. Thanks go to all the sponsors of the event: Macfarlanes LLP, the British Medical Association, Health Protection Research Unit in Emerging and Zoonotic Infections (HPRU EZI) at University of Liverpool, Public Health England in collaboration with Liverpool School of Tropical Medicine; Elysium Neurological, Routledge, PLG, the Guarantors of Brain.
If you are interested in attending Encephalitis Conference 2019 this will be held at the Royal College of Physicians, London on Monday 2nd December, 2019. You can be assured of receiving a notification of registration for the conference along with opportunities for research funding by signing up to be a professional member: www.encephalitis.info/ professional-membership