The DexEnceph study is the most definitive evidence so far on whether corticosteroids should be used alongside antiviral drug aciclovir for severe brain infections. A UK clinical trial has shown that the corticosteroid dexamethasone, along with standard antiviral treatment for encephalitis caused by herpes simplex virus (HSV), does not improve long-term outcomes overall. However, early use may lead to better recovery, and the treatment is safe for patients in whom encephalitis is suspected.
The 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 crucial data on managing this severe 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.
Key Study Findings
- Enrollment: The multi-centre, randomised, observer-blind Phase 3 trial enrolled 94 patients across 53 NHS hospitals.
- Methodology: Participants received either dexamethasone plus aciclovir or aciclovir alone.
- Primary Outcome: Verbal memory at 26 weeks, assessed using the Wechsler Memory Scale, showed no significant difference overall between the two groups.
- Safety & Potential: An exploratory analysis showed that when steroids were given earlier in the course of illness, patients tended to do better. Importantly, the trial demonstrated that dexamethasone is safe for patients with HSV encephalitis.
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). The trial results are published today (21 January 2026) in the Lancet Neurology.
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.
