Major clinical trial provides definitive evidence of impacts of steroid treatment on severe brain infection

A major UK clinical trial has shown that adding the corticosteroid dexamethasone to standard antiviral treatment for encephalitis (brain inflammation), caused by herpes simplex virus (HSV) does not improve long-term outcomes overall, although early use may lead to better recovery, and the treatment is safe for patients in whom encephalitis is suspected.

Transmission electron micrograph of herpes simplex virus. Some nucleocapsids are empty, as shown by penetration of electron-dense stain.

The DexEnceph study, 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, 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.

HSV encephalitis is the most common sporadic viral encephalitis worldwide. Although aciclovir has transformed survival since the 1970s, many survivors are left with long-term cognitive difficulties, especially memory problems.

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 (21 January 2026) in the Lancet Neurology.

No overall benefit but earlier treatment may improve outcomes

The multi-centre, randomised, observer blind phase 3 trial enrolled 94 patients across 53 NHS hospitals. Participants received either dexamethasone plus aciclovir or aciclovir alone. The primary outcome, verbal memory at 26 weeks, assessed using the Wechsler Memory Scale, showed no significant difference overall between the two groups.

Although dexamethasone did not improve overall outcomes, an exploratory analysis showed that when steroids were given earlier in the course of illness, patients tended to do better. The trial also demonstrated that dexamethasone is safe for patients with HSV encephalitis.

Corticosteroids are already used in other inflammatory brain diseases, such as autoimmune encephalitis. Evidence that dexamethasone is safe in HSV encephalitis suggests it could be considered early in all patients with suspected encephalitis, before the cause is confirmed.

Labour of love

Professor Tom Solomon CBE, Chief Investigator of DexEnceph and Director of The Pandemic Institute, 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.”

Landmark trial

Dr Ava Easton, 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.”

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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.”