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September 6, 2010

Challenge of the unknown
A systematic review of acute encephalitis in non-outbreak situations

J. Granerod, MSc, C.C. Tam, PhD, N.S. Crowcroft, MD, N.W.S. Davies, PhD, MBBS, M. Borchert, MD, PhD, and S.L. Thomas, MBBS, PhDAuthors Info & Affiliations
September 7, 2010 issue
75 (10) 924-932
https://doi.org/10.1212/WNL.0b013e3181f11d65
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Abstract

Background: The threat of emerging infections and recognition of novel immune-mediated forms of encephalitis has raised the profile of this condition in recent years. Incidence is poorly defined and most cases have an unknown cause. There is currently much interest in identification of new microbial agents of encephalitis, but no work has investigated systematically reasons for lack of pathogen identification in studies.
Methods: We systematically reviewed published literature on incidence and etiology of encephalitis in non-outbreak settings and explored possible explanations for the large number of cases of unknown etiology.
Results: Annual incidence ranged from 0.07 to 12.6 cases per 100,000 population with an evident decrease over time (p = 0.01). The proportion of cases with unknown etiology was high across studies (>50% in 26 of 41 studies), with strong evidence of heterogeneity in study findings (p < 0.001). Our meta-regression identified study period, setting, and subsyndrome to be the main contributors to between-study variation, rather than methodologic factors such as study design, case definitions, sample types, and testing strategies.
Conclusions: Our findings support the hypothesis that new and emerging infectious agents, or new forms of immune-mediated encephalitis, may be responsible for cases currently of unknown cause and encourage the ongoing global effort to identify these. Our review highlights research areas that might lead to a better understanding of the causes of encephalitis and ultimately reduce the morbidity and mortality associated with this devastating condition.

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Information & Authors

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Published In

Neurology®
Volume 75 • Number 10 • September 7, 2010
Pages: 924-932
PubMed: 20820004

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© 2010.

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Published online: September 6, 2010
Published in print: September 7, 2010

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Keyword

  1. ADEM = acute disseminated encephalomyelitis; CI = confidence interval; HSV = herpes simplex virus; JEV = Japanese encephalitis virus; NMDAR = N-methyl-d-aspartate receptor; TBEV = tick-borne encephalitis virus; VGKC = voltage-gated potassium channels; VZV = varicella zoster virus.

Authors

Affiliations & Disclosures

J. Granerod, MSc
From the Health Protection Agency Centre for Infections (J.G.), Virus Reference Department, London; London School of Hygiene and Tropical Medicine (C.C.T., M.B., S.L.T.), London, UK; Ontario Agency for Health Protection and Promotion (N.S.C.), Canada; and Department of Neurology (N.W.S.D.), St. Vincent's Hospital & University of New South Wales, Sydney, Australia.
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C.C. Tam, PhD
From the Health Protection Agency Centre for Infections (J.G.), Virus Reference Department, London; London School of Hygiene and Tropical Medicine (C.C.T., M.B., S.L.T.), London, UK; Ontario Agency for Health Protection and Promotion (N.S.C.), Canada; and Department of Neurology (N.W.S.D.), St. Vincent's Hospital & University of New South Wales, Sydney, Australia.
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N.S. Crowcroft, MD
From the Health Protection Agency Centre for Infections (J.G.), Virus Reference Department, London; London School of Hygiene and Tropical Medicine (C.C.T., M.B., S.L.T.), London, UK; Ontario Agency for Health Protection and Promotion (N.S.C.), Canada; and Department of Neurology (N.W.S.D.), St. Vincent's Hospital & University of New South Wales, Sydney, Australia.
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N.W.S. Davies, PhD, MBBS
From the Health Protection Agency Centre for Infections (J.G.), Virus Reference Department, London; London School of Hygiene and Tropical Medicine (C.C.T., M.B., S.L.T.), London, UK; Ontario Agency for Health Protection and Promotion (N.S.C.), Canada; and Department of Neurology (N.W.S.D.), St. Vincent's Hospital & University of New South Wales, Sydney, Australia.
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M. Borchert, MD, PhD
From the Health Protection Agency Centre for Infections (J.G.), Virus Reference Department, London; London School of Hygiene and Tropical Medicine (C.C.T., M.B., S.L.T.), London, UK; Ontario Agency for Health Protection and Promotion (N.S.C.), Canada; and Department of Neurology (N.W.S.D.), St. Vincent's Hospital & University of New South Wales, Sydney, Australia.
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S.L. Thomas, MBBS, PhD
From the Health Protection Agency Centre for Infections (J.G.), Virus Reference Department, London; London School of Hygiene and Tropical Medicine (C.C.T., M.B., S.L.T.), London, UK; Ontario Agency for Health Protection and Promotion (N.S.C.), Canada; and Department of Neurology (N.W.S.D.), St. Vincent's Hospital & University of New South Wales, Sydney, Australia.
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Notes

Address correspondence and reprint requests to Ms. J. Granerod, Health Protection Agency Centre for Infections, Virus Reference Department, 61 Colindale Avenue, London NW9 5EQ, UK [email protected]

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