Safety and Efficacy of Adjunct Dexamethasone in Adults with Herpes Simplex Virus Encephalitis in The UK - Part 1

In part one of this series, Dr. Aaron Zelikovich discusses the trial design and primary results. 

Show citation: 

Solomon T, Hooper C, Easton A, et al. Safety and efficacy of adjunct dexamethasone in adults with herpes simplex virus encephalitis in the UK (DexEnceph): a multicentre, observer-blind, randomised, phase 3, controlled trial. Lancet Neurol. 2026;25(2):136-146. doi:10.1016/S1474-4422(25)00454-5 

Show transcript: 

Dr. Aaron Zelikovich: 

Welcome to today's Neurology Minute. My name is Aaron Zelikovich. I'm a neuromuscular specialist at Lenox Hill Hospital in New York City. Today, we'll discuss part one of a three-part series reviewing a recent article titled Safety and Efficacy of Adjunct Dexamethasone in Adults with Herpes Simplex Virus Encephalitis in the United Kingdom (DexEnceph) Study, a multicenter observer-blind randomized phase three control trial published in Lancet Neurology.

In the first episode, we'll focus on the trial design and primary results. In part two, we'll discuss the clinical implications for patients with HSV encephalitis, and in part three, discuss the outcomes seen across the trial during and after an acute infection. Overall, the study found that adjunct dexamethasone did not improve outcomes in patients with CSF-confirmed HSV encephalitis. But importantly, it also did not worsen outcomes. Prior research that was non-randomized and retrospective of 45 patients with HSV encephalitis found that patients did not receive corticosteroids had worse outcomes.

A different randomized trial looking at dexamethasone and HSV encephalitis was only able to recruit 41 patients and was stopped prematurely due to the lack of recruitment. Prior to the study, there was no clear evidence that adjunct steroids with acyclovir improved outcomes in HSV encephalitis. The Dex and phase three randomized clinical trial performed in the United Kingdom at 53 hospitals recruited patients from 2016 to 2022. They screened over 1,400 patients of which only 94, or 6%, were enrolled. Patients were randomized to either acyclovir only or acyclovir and intravenous dexamethasone. In order to be randomized, patients had to have a febrile illness with new onset seizure or new focal neurological sign or altered mental status as well as a positive HSV type one or two PCR from the CSF.

The primary outcome for this study was the Wechsler Memory Scale Type Four Auditory Memory Index Score which was collected at 26 weeks. It had a range of 40, which is the worst outcome, to a range of 160 which was considered normal. 81 patients were included in the modified intention-to-treat analysis. Of the 13 patients, six were lost to follow-up, and seven withdrew consent. There were 39 patients in the dexamethasone group and 42 in the acyclovir-only group in the final analysis.

The primary outcome of the Wechsler Memory Scale had similar scores in both groups. 71 in the dexamethasone group and 69 in the control group with a P value of 0.76. The safety profile was similar in both groups, and there were no additional safety signals found in the dexamethasone-treated group. At 26 weeks, there were 12 deaths from HSV encephalitis, six from each group, as well as a similar time to discharge between both cohorts. The DexEnceph clinical trial did not show any clear clinical benefit for dexamethasone with regards to clinical outcomes but also didn't show any increased safety concerns compared to only acyclovir.

In part two, we will discuss the implications of this trial in patients with undifferentiated encephalitis and the role that steroids play in patients that HSV encephalitis is suspected.

Thank you so much, and have a wonderful day.