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NMDAR-antibody encephalitis is a life-threatening neuropsychiatric condition, with symptoms including seizures and movement disorders. Because its early symptoms include psychiatric disturbance, such as hallucinations, and the fact it often appears in young people, the initial clinical impression may be of a psychosis, which has different treatment approaches to encephalitis.
NMDAR-antibody encephalitis can only be definitively diagnosed by sampling cerebrospinal fluid (CSF) through a procedure called lumbar puncture. While safe, lumbar puncture is more invasive than blood tests and not offered by most mental health services, instead usually requiring a neurology team to review and consider carrying out the procedure.
To help facilitate this clinical conversation, an international collaborative team of scientists and clinicians led by Dr Adam Al-Diwani at the University of Oxford, supported by the National Institute of Health and Care Research (NIHR) Oxford Health Biomedical Research Centre, Professor Daniel Joyce, Co-Director at the NIHR Mental Health Research for Innovation Centre at the University of Liverpool and Mersey Care NHS Foundation Trust, and Professor Sarosh Irani at Mayo Clinic Florida, have identified features and suggest a scoring system that could help doctors in frontline medical and mental health services identify in which patients CSF sampling should be considered.
The research team, including colleagues from across Europe and the United States, compared the symptoms of 100 episodes of NMDAR-antibody encephalitis with 145 of psychosis including those from early intervention services in the UK. The findings have been published in The Lancet Psychiatry.
They found that unlike for most psychoses, the mental state changes in NMDAR-antibody encephalitis had a very quick onset, within days, with symptoms escalating from changes in mood to psychosis and catatonia in a fortnight.
The team then provided evidence that an existing ‘autoimmune psychosis’ approach which is weighted on this rapid onset together with overt neurological features and catatonia can help refine diagnosis. They also complement this with a scoring system focused on the mental state, which prior to neurological features emerging, can be the only clinical feature to guide clinicians. Overall, they suggest that their findings are compatible with a growing impression in the field that delirium, a disorder usually seen in older people after infections which shares abrupt changes in cognition and mental state, is likely a better fit than psychosis for this psychiatric onset of NMDAR-antibody encephalitis. This unusual ‘young delirium’ may be a useful memory aid for frontline clinicians.
Lead author Dr Al-Diwani, Senior Clinical Researcher in the Department of Psychiatry at Oxford and Honorary Consultant Psychiatrist at Oxford Health NHS Foundation Trust, said:
NMDAR-antibody encephalitis is a very serious illness and outcomes are linked to timeliness of treatment, with immunological therapies and neurological monitoring. So whether it is A&E doctors, psychiatrists, or neurologists; we all have a part to play in ensuring we consider this condition as a cause of new changes in mental state.
However, this is not easy, particularly since psychotic disorders are far more common than NMDAR-antibody encephalitis. There is evidence of both over-suspicion, where people undergo unnecessary tests; but also under-diagnosis, where the condition is not picked up quickly enough, or at all. Getting this balance right is an ongoing conversation and we hope with this work, we add evidence to help guide planning of clinical systems.
This study suggests that NMDAR-antibody encephalitis drives changes in mental state that are generally very rapid with then a complex and evolving picture. This should complement existing approaches anchored in recognising the combination of these psychiatric features with neurological features such as seizures and abnormal movements. While our score is simple to action, it now needs to be evaluated in future prospective studies in diverse settings.”
The team also advocate that lumbar punctures are more easily available to deliver in psychiatric units, such as through liaison neurology and regional multidisciplinary neuro-immunology teams, as pioneered in Oxford Health NHS Foundation Trust and NIHR Oxford Health Biomedical Research Centre.
The study team included scientists from University of Oxford Departments of Psychiatry, Experimental Psychology and the Nuffield Department of Clinical Neuroscience, NHS Trusts including Oxford Health NHS Foundation Trust, and scientists from across the UK, Europe, including Charite Universttatsmedizin Berlin, and the US.