Study pinpoints major causes of encephalitis in the UK, but many patients are undiagnosed and difficult to treat

October 17, 2010

Less than half of encephalitis cases in England have a proven infectious cause, of these herpes simplex virus and varicella zoster virus are the most common causes. Immune-mediated disease, in which the body's immune system mistakenly attacks the brain, is responsible for about a fifth of cases. But the cause of encephalitis remains unidentified in over a third of patients who have a poor prognosis. The Article published Online First in The Lancet Infectious Diseases, calls for more research into the causes of encephalitis to ensure early diagnosis and timely treatment to improve outcomes in these patients. This is especially important because of concerns about new and emerging triggers.

There are an estimated 700 cases of viral encephalitis in the England each year. Encephalitis starts as a flu-like illness and can progress to a fatal inflammation of the brain. Even if infection is not fatal, patients often develop movement disorders, muscle weakness, tremors, confusion, and paralysis. Encephalitis has many causes, but for up to 85% of patients worldwide the cause is not known. Early and accurate diagnosis is vital to ensure appropriate treatment is given on time and to improve prognosis.

In this study, Julia Granerod from the Health Protection Agency, London, UK and colleagues investigated the different causes of encephalitis in patients in the UK.

203 patients with suspected encephalitis were recruited over 2 years from 24 hospitals across England. Extensive PCR and antibody testing were done for all common causes of infectious encephalitis (e.g. herpes simplex, measles and mumps), less common causes in immunocompromised patients (e.g. HIV, Epstein-Barr virus), and travel-related causes (e.g. West Nile virus, rabies). Patients were also tested for non-infectious triggers including autoimmunity and followed for 6 months after leaving hospital.

Overall, a cause was identified in 63% of patients. Infections accounted for 42% of cases, the most common were herpes simplex (19%), varicella zoster virus (5%), and Mycobacterium tuberculosis (5%). An underlying immune-mediated cause was diagnosed in 42 (21%) patients.

A total of 24 (12%) patients died, which is higher than the 7% previously reported in England for viral encephalitis. Patients infected with M tuberculosis and varicella zoster virus had the highest fatalities.

Despite just 37% of cases having an unknown cause, the proportion of cases with unknown cause was higher than that for any specific identified cause. The authors say: "The poor outcome we report in those for whom a cause could not be identified emphasises the importance of further research to define causality in these patients."

They point out: "Prompt distinction between causes of acute encephalitis is essential to direct appropriate management. We confirmed the well described clinical findings for viral, bacterial, and mycobacterial causes. However, no single presenting symptom, sign, or cerebrospinal fluid (CSF) measurement could alone or in combination accurately separate one group from another."

In a Comment, Jean-Paul Stahl from Joseph Fourier University and Alexandra Mailles from the Institut de Veille Sanitaire in France say: "More research is also needed to investigate the pathological causes and mechanisms, as well as the prognosis, to provide improved management for patients. Although encephalitis is an acute infection, this disease is a long-term neurological challenge for most patients."
Dr Julia Granerod, Health Protection Agency, London, UK. Via HPA Centre for Infections press office T) +44 (0)20 8327 6647 E)

Professor Jean-Paul Stahl, Joseph Fourier University and University Hospital, Grenoble, France. T) + 33 476 765 291 or + 33 607 557 977 (mobile) E)

For full Article and Comment, see:



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