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Clinical Predictors of Encephalitis in UK Adults – A Multi-Centre Prospective Observational Cohort Study

27 Pages Posted: 14 Jun 2021

See all articles by Sylviane Defres

Sylviane Defres

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences

Kukatharmini Tharmaratnam

University of Liverpool - Department of Health Data Scienc

Benedict Michael

University of Liverpool - Institute of Infection and Global Health

Mark Ellul

University of Liverpool - Institute of Infection and Global Health

Nicholas W S Davies

Chelsea and Westminster Hospital - Department of Neurology

Ava Easton

Encephalitis Society

Michael J. Griffiths

University of Liverpool

Maneesh Bhojak

The Walton Centre NHS Foundation Trust

Kumar Das

The Walton Centre NHS Foundation Trust - Department of Neurology

Hayley Hardwick

University of Liverpool

Christopher Cheyne

University of Liverpool - Department of Health Data Science

Rachel Kneen

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences; Alder Hey Children's NHS Foundation Trust

Antonieta Medina-Lara

University of Exeter - Health Economics Group

Anne Christine Salter

Encephalitis Society

Nicholas J. Beeching

Liverpool University Hospitals NHS Foundation Trust (LUH) - Tropical and Infectious Disease Unit

Enitan Carrol

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences

Angela Vincent

University of Oxford

ENCEPH UK Study Group

Independent

Marta Garcia-Finana

University of Liverpool - Department of Health Data Science

Tom Solomon

University of Liverpool - Institute of Infection and Global Health

More...

Abstract

Background: Encephalitis, brain inflammation and swelling, most often caused by an infection or the body’s immune defences, can have devastating consequences, especially if diagnosed late. We looked for clinical predictors of different types of encephalitis to help clinicians consider earlier treatment.

Methods: We conducted a multicentre prospective observational cohort study (ENCEPH-UK) of adults (> 16 years) with suspected encephalitis at 31 UK hospitals. We evaluated clinical features and investigated for infectious and autoimmune causes.

Findings: 341 patients were enrolled between December 2012 and December 2015 and followed up for 12 months. 233 had encephalitis, of whom 65 (28%) had herpes simplex virus (HSV), 38 (16%) had confirmed or probable autoimmune encephalitis, and 87 (37%) had no cause found. The median time from admission to 1st dose of aciclovir for those with HSV was 14 hours (IQR 5-50); time to 1st dose of immunosuppressant for the autoimmune group was 125 hours (IQR 45-250). Compared to non-HSV encephalitis, patients with HSV more often had fever, lower serum sodium and lacked a rash. Those with probable or confirmed autoimmune encephalitis were more likely to be female, have abnormal movements, normal serum sodium levels and a cerebrospinal fluid white cell count < 20 cells x106/L, but they were less likely to have a febrile illness.

Interpretation: Initiation of treatment for autoimmune encephalitis is delayed considerably compared with HSV encephalitis. Clinical features can help identify patients with autoimmune disease and could be used to initiate earlier presumptive therapy.

Clinical Trial Registration Details:

Funding Information: National Institute for Health Research, UK.

Declaration of Interests: None to declare.

Ethics Approval Statement: The study protocols were approved by participating sites and the National Research Ethics Service (now part of the Health Research Authority) East Midlands Nottingham 1 committee (reference 11/EM/0442). Written consent for entry into the study was obtained from patients or an accompanying relative.

Keywords: Encephalitis, autoimmune, herpes simplex virus, infectious, clinical predictors

Suggested Citation

Defres, Sylviane and Tharmaratnam, Kukatharmini and Michael, Benedict and Ellul, Mark and Davies, Nicholas W S and Easton, Ava and Griffiths, Michael J. and Bhojak, Maneesh and Das, Kumar and Hardwick, Hayley and Cheyne, Christopher and Kneen, Rachel and Medina-Lara, Antonieta and Salter, Anne Christine and Beeching, Nicholas J. and Carrol, Enitan and Vincent, Angela and Group, ENCEPH UK Study and Garcia-Finana, Marta and Solomon, Tom, Clinical Predictors of Encephalitis in UK Adults – A Multi-Centre Prospective Observational Cohort Study. Available at SSRN: https://ssrn.com/abstract=3859285 or http://dx.doi.org/10.2139/ssrn.3859285

Sylviane Defres

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences ( email )

United Kingdom

Kukatharmini Tharmaratnam

University of Liverpool - Department of Health Data Scienc

Chatham Street
Brownlow Hill
Liverpool, L69 7ZA
United Kingdom

Benedict Michael

University of Liverpool - Institute of Infection and Global Health ( email )

8 West Derby Street
Liverpool, L69 7BE
United Kingdom

Mark Ellul

University of Liverpool - Institute of Infection and Global Health ( email )

8 West Derby Street
Liverpool, L69 7BE
United Kingdom

Nicholas W S Davies

Chelsea and Westminster Hospital - Department of Neurology

London
United Kingdom

Ava Easton

Encephalitis Society ( email )

Michael J. Griffiths

University of Liverpool

Chatham Street
Brownlow Hill
Liverpool, L69 7ZA
United Kingdom

Maneesh Bhojak

The Walton Centre NHS Foundation Trust

Kumar Das

The Walton Centre NHS Foundation Trust - Department of Neurology

Hayley Hardwick

University of Liverpool

Chatham Street
Brownlow Hill
Liverpool, L69 7ZA
United Kingdom

Christopher Cheyne

University of Liverpool - Department of Health Data Science

Chatham Street
Brownlow Hill
Liverpool, L69 7ZA
United Kingdom

Rachel Kneen

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences ( email )

Liverpool
United Kingdom

Alder Hey Children's NHS Foundation Trust

Liverpool
United Kingdom

Antonieta Medina-Lara

University of Exeter - Health Economics Group ( email )

Northcote House
The Queen's Drive
Exeter, Devon EX4 4QJ
United Kingdom

Anne Christine Salter

Encephalitis Society

Nicholas J. Beeching

Liverpool University Hospitals NHS Foundation Trust (LUH) - Tropical and Infectious Disease Unit ( email )

United Kingdom

Enitan Carrol

University of Liverpool - Institute of Infection, Veterinary and Ecological Sciences

Angela Vincent

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

ENCEPH UK Study Group

Independent

Marta Garcia-Finana

University of Liverpool - Department of Health Data Science

Chatham Street
Brownlow Hill
Liverpool, L69 7ZA
United Kingdom

Tom Solomon (Contact Author)

University of Liverpool - Institute of Infection and Global Health ( email )

8 West Derby Street
Liverpool, L69 7BE
United Kingdom

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