Neuropsychological and psychiatric outcomes in encephalitis: A multi-centre case-control study

ENCEPH UK study group, Lara Harris, Julia Griem, Alison Gummery, Laura Marsh, Sylviane Defres, Maneesh Bhojak, Kumar Das, Ava Easton, Tom Solomon, Michael Kopelman, David Brown, Julia Granerod

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11 Citations (Scopus)


Objectives Our aim was to compare neuropsychological and psychiatric outcomes across three encephalitis aetiological groups: Herpes simplex virus (HSV), other infections or autoimmune causes (Other), and encephalitis of unknown cause (Unknown).

Methods Patients recruited from NHS hospitals underwent neuropsychological and psychiatric assessment in the short-term (4 months post-discharge), medium-term (9-12 months after the first assessment), and long-term (>1-year). Healthy control subjects were recruited from the general population and completed the same assessments.

Results Patients with HSV were most severely impaired on anterograde and retrograde memory tasks. In the short-term, they also showed executive, IQ, and naming deficits, which resolved in the long-term. Patients with Other or Unknown causes of encephalitis showed moderate memory impairments, but no significant impairment on executive tests. Memory impairment was associated with hippocampal/medial temporal damage on magnetic resonance imaging (MRI), and naming impairment with left temporal and left frontal abnormalities. Patients reported more subjective cognitive complaints than healthy controls, with tiredness a significant problem, and there were high rates of depression and anxiety in the HSV and the Other encephalitis groups. These subjective, self-reported complaints, depression, and anxiety persisted even after objectively measured neuropsychological performance had improved.

Conclusions Neuropsychological and psychiatric outcomes after encephalitis vary according to aetiology. Memory and naming are severely affected in HSV, and less so in other forms. Neuropsychological functioning improves over time, particularly in those with more severe short-term impairments, but subjective cognitive complaints, depression, and anxiety persist, and should be addressed in rehabilitation programmes.

Original languageEnglish
Article numbere0230436
JournalPLoS ONE
Issue number3
Publication statusPublished - 25 Mar 2020

Bibliographical note

Funding Information: This article is independent research funded by the National Institute for Health Research ( under its Programme Grants for Applied Research Programme (grant reference number RP-PG-0108-10,048). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England. TS is supported by the National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections, NIHR Global Health Research Group on Brain Infections (number 17/63/110), and the European Union's Horizon 2020 research and innovation program ZikaPLAN (Preparedness Latin America Network), grant agreement No. 734584. MDK was supported by the Biomedical Research Centre (BRC) of the Institute of Psychiatry, Psychology and Neuroscience and the South London and Maudsley NHS Foundation Trust, as well as King’s College London. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Open Access: This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publisher copyright: © 2020 Harris et al

Citation: Harris L, Griem J, Gummery A, Marsh L, Defres S, et al. (2020) Neuropsychological and psychiatric outcomes in encephalitis: A multi-centre case-control study. PLOS ONE 15(3): e0230436.



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