Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study - 04/08/11

Doi : 10.1016/S1473-3099(10)70222-X

Julia Granerod, MSc ^a,^⁎ , Helen E Ambrose, DPhil ^a, Nicholas WS Davies, PhD ^b, Jonathan P Clewley, PhD ^a, Amanda L Walsh, MSc ^a, Dilys Morgan, MD ^a, Richard Cunningham, FRCPath ^c, Mark Zuckerman, FRCPath ^d, Ken J Mutton, MBBS ^e, Tom Solomon, ProfFRCP ^f,^g, Katherine N Ward, PhD ^h, Michael PT Lunn, FRCP ⁱ, Sarosh R Irani, MRCP ^j, Angela Vincent, ProfFRCPath ^j, David WG Brown, ProfFRCPath ^a, Natasha S Crowcroft, MD ^a,^k

on behalf of the UK Health Protection Agency (HPA) Aetiology of Encephalitis Study Group

^a Centre for Infections, Health Protection Agency, London, UK

^b St Vincent’s Hospital and University of New South Wales, Sydney, Australia

^c Plymouth Hospitals National Health Service Trust, Plymouth, UK

^d King’s College Hospital, London, UK

^e Manchester Royal Infirmary, Manchester, UK

^f Institute of Infection and Global Health, University of Liverpool, Liverpool, UK

^g Department of Neurology, Walton Neuroscience Centre NHS Foundation Trust, Liverpool, UK

^h University College Hospital, London, UK

ⁱ National Hospital for Neurology and Neurosurgery, London, UK

^j Department of Clinical Neurology, John Radcliffe Hospital, Oxford, UK

^k Ontario Agency for Health Protection and Promotion, Toronto, Canada

^* Correspondence to: Julia Granerod, Health Protection Agency Centre for Infections, Virus Reference Department, 61 Colindale Avenue, London NW9 5EQ, UK

Summary

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.