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Cited by 1,358Infectious Encephalopathies and EncephalitisAutoimmune Neurological Disorders and TreatmentsViral Infections and Immunology Research

Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study

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Granerod, Julia, Ambrose, Helen E, Davies, Nicholas WS, Clewley, Jonathan P, Walsh, Amanda L, Morgan, Dilys, Cunningham, Richard, Zuckerman, Mark +8 more·2010·The Lancet Infectious Diseases
DOI 10.1016/s1473-3099(10)70222-x
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Abstract

BACKGROUND: Encephalitis has many causes, but for most patients the cause is unknown. We aimed to establish the cause and identify the clinical differences between causes in patients with encephalitis in England. METHODS: Patients of all ages and with symptoms suggestive of encephalitis were actively recruited for 2 years (staged start between October, 2005, and November, 2006) from 24 hospitals by clinical staff. Systematic laboratory testing included PCR and antibody assays for all commonly recognised causes of infectious encephalitis, investigation for less commonly recognised causes in immunocompromised patients, and testing for travel-related causes if indicated. We also tested for non-infectious causes for acute encephalitis including autoimmunity. A multidisciplinary expert team reviewed clinical presentation and hospital tests and directed further investigations. Patients were followed up for 6 months after discharge from hospital. FINDINGS: We identified 203 patients with encephalitis. Median age was 30 years (range 0-87). 86 patients (42%, 95% CI 35-49) had infectious causes, including 38 (19%, 14-25) herpes simplex virus, ten (5%, 2-9) varicella zoster virus, and ten (5%, 2-9) Mycobacterium tuberculosis; 75 (37%, 30-44) had unknown causes. 42 patients (21%, 15-27) had acute immune-mediated encephalitis. 24 patients (12%, 8-17) died, with higher case fatality for infections from M tuberculosis (three patients; 30%, 7-65) and varicella zoster virus (two patients; 20%, 2-56). The 16 patients with antibody-associated encephalitis had the worst outcome of all groups-nine (56%, 30-80) either died or had severe disabilities. Patients who died were more likely to be immunocompromised than were those who survived (OR = 3·44). INTERPRETATION: Early diagnosis of encephalitis is crucial to ensure that the right treatment is given on time. Extensive testing substantially reduced the proportion with unknown cause, but the proportion of cases with unknown cause was higher than that for any specific identified cause. FUNDING: The Policy Research Programme, Department of Health, UK.

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  • Epidemiological studies suggest that anti-NMDAR encephalitis is the most common cause of autoimmune encephalitis after acute demyelinating encephalomyelitis (ADEM).

    “Epidemiological studies suggest that this disorder is the most common cause of autoimmune encephalitis after acute demyelinating encephalomyelitis (ADEM).5”

    From Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study (2013) · cites this paper as [5]

    The Discussion (page unavailable) says that about a fifth of patients had immune-mediated encephalitis, mostly ADEM, and reports 16 antibody-associated cases. The Results (page unavailable) identify NMDA receptor antibodies among the causes, but the passages do not establish that anti-NMDAR encephalitis was more common than the other antibody-associated cause after ADEM. (LLM, conf=0.78)

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Authors
Granerod, J., Ambrose, H. E., Davies, N. W., Clewley, J. P., Walsh, A. L., Morgan, D., Cunningham, R., Zuckerman, M., Mutton, K. J., Solomon, T., Ward, K. N., Lunn, M. P., Irani, S. R., Vincent, A., Brown, D. W., & Crowcroft, N. S.
Affiliations
  • Health Protection Agency (GB)
  • UNSW Sydney (AU)
  • National Health Service (GB)
  • King's College Hospital (GB)
  • Manchester Royal Infirmary (GB)
  • University of Liverpool (GB)
  • University College Hospital (GB)
  • John Radcliffe Hospital (GB)
ORCID
Venue
The Lancet Infectious Diseases
Publisher
Elsevier BV
Published
2010-12
Volume
10
Issue
12
Pages
835-844
ISSN
1473-3099 (ISSN-L)
DOI
10.1016/s1473-3099(10)70222-x
OpenAlex
W2092406095
Cited by
1,358
References
1
Citations by year
2026: 65 · 2025: 79 · 2024: 77 · 2023: 92 · 2022: 103 · 2021: 106 · 2020: 97 · 2019: 119 · 2018: 97 · 2017: 91 · 2016: 98 · 2015: 88 · 2014: 68 · 2013: 65 · 2012: 62
FWCI
33.16
Type
journal article
Language
en
Update notices
erratum (2011-02-01)
Open access
Licence
Locations
  • The Lancet Infectious Diseases (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
  • Encephalitis Society
  • National Institute for Health Research
  • University College London Hospitals NHS Foundation Trust
  • Department of Health, Australian Government
Topics
  • Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
  • Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
Keywords
encephalitis, infectious encephalitis, herpes simplex virus, varicella-zoster virus, Mycobacterium tuberculosis, immune-mediated encephalitis, case fatality, immunocompromised patients, clinical features, diagnostic testing, autoimmune encephalitis
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Communicable Diseases, Encephalitis, England, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Prospective Studies, Regression Analysis, Multivariate Analysis, Young Adult

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