Do corticosteroids improve outcomes in herpes simplex virus (HSV) encephalitis?

A major UK clinical trial – DexEnceph study – provides the most definitive evidence so far on whether corticosteroids should be used alongside antiviral drug aciclovir for this severe, potentially life changing brain infection. The study was led by researchers at The Pandemic Institute, the University of Liverpool, and Walton Centre NHS Foundation Trust in partnership with Encephalitis International and research teams around the country.

HSV encephalitis is the most common type of viral encephalitis worldwide. Aciclovir is the standard treatment for anyone with this type of encephalitis. However, despite treatment, some patients are left with significant loss of memory among may other difficulties.

In total, 94 patients with HSV encephalitis were recruited for this study. The research team divided the patients into two groups – one that received corticosteroids (dexamethasone) four times a day for four days and the other that did not. Both groups also received aciclovir as part of their treatment.

This trial has shown that adding the corticosteroids to standard antiviral treatment does not improve long-term outcomes overall, although early use may lead to better recovery.  The trial also demonstrated that dexamethasone is safe for patients with HSV encephalitis which suggests it could be considered early in all patients with suspected encephalitis, before the cause is confirmed.

Professor Tom Solomon CBE, Chief Investigator of DexEnceph, Director of The Pandemic Institute, President of Encephalitis International said: “For decades people have wondered whether corticosteroids would improve the outcome of herpes simplex virus encephalitis, or perhaps make things worse because of their immunosuppressive effects. Increasingly, when patients present with encephalitis, clinicians want to give corticosteroids in case it is an autoimmune encephalitis, but until they have ruled out herpes simplex virus encephalitis they have not felt it was safe to do so.

This study shows that if you suspect a patient has encephalitis which might be autoimmune or could be HSV, it is safe to give steroids. The fact that early corticosteroid use seems to be associated with improved outcome may well encourage doctors to do this as soon as they see the patient.

This trial has been a labour of love. We are deeply grateful to the clinicians across the country who contributed patients, and to the patients and their families who took part. The European guidelines on encephalitis are being revised and we expect they will support earlier use of corticosteroids in patients with suspected encephalitis.”

Dr Ava Easton MBE, Chief Executive of Encephalitis International, said: “People living with the consequences of encephalitis urgently need better treatments. This landmark trial shows what works and what does not. We are proud to have supported this effort and to see a question that has puzzled clinicians for decades finally answered.”

Dr Mark Ellul, Clinical Lecturer at University of Liverpool and Consultant Neurologist said: “For clinicians seeing acutely unwell patients, HSV encephalitis is one of the most devastating neurological emergencies we face. DexEnceph addresses a long-standing area of uncertainty in day-to-day practice, providing evidence to guide treatment in the crucial first days of illness. Just as importantly, this trial shows that it is possible to deliver high-quality randomised studies in acute, life-threatening neurological diseases through national collaboration.

For patients and families affected by HSV encephalitis, this represents a meaningful step towards improving outcomes and standardising care based on evidence rather than assumption.”

The DexEnceph study was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a partnership between the National Institute for Health and Care Research (NIHR) and the UKRI Medical Research Council (MRC), and the trial results are published today (21 January 2026) in the Lancet Neurology.

Click here to read the full article in The Lancet Neurology.