The evidence on steroids in herpes encephalitis is 209 patients deep

Design

systematic review and meta-analysis; randomised and observational evidence pooled separately, random-effects methods

Population

209 patients with herpes simplex encephalitis across 4 comparative studies (2 randomised, 2 retrospective)

Primary outcome

unfavourable global neurological or functional outcome; all-cause mortality

Effect

unfavourable outcome RR 1.00 (95% CI 0.68-1.47); mortality RR 0.92 (0.35-2.40); serious adverse events RR 1.14 (0.54-2.44)

A systematic review searched to July 2026 for studies of systemic corticosteroids added to antiviral therapy in herpes simplex encephalitis. It found four comparative studies covering 209 patients: two randomised trials and two retrospective series. Aciclovir was the background antiviral wherever the regimen was specified.

Pooling the randomised data gave no difference in unfavourable global outcome (RR 1.00, 95% CI 0.68-1.47), mortality (RR 0.92, 0.35-2.40), serious adverse events (RR 1.14, 0.54-2.44) or seizures during follow-up (RR 0.73, 0.33-1.62). Barthel Index differences were inconclusive at six months (3.05 points, −6.99 to 13.09) and at discharge. In DexEnceph, cerebrospinal fluid HSV DNA was still detectable at around day 14 in 4 of 36 dexamethasone recipients against 9 of 43 controls, and five relapses were reported with dexamethasone against none with control — too few events to attribute.

The conclusion is narrower than 'steroids do not work'. What the data support is that there is no basis for giving them routinely to unselected patients, and no data at all on the situation where they are most often reached for: life-threatening cerebral oedema. If you give dexamethasone to a patient with herpes encephalitis and midline shift, you are making a decision the literature has not examined, and it is worth recording it as such.

• Start aciclovir on suspicion; nothing in this changes the antiviral priority or its timing
• Do not add corticosteroids as routine adjunctive therapy
• Where raised intracranial pressure forces the decision, document that you are treating oedema rather than following evidence for the infection
• Repeat CSF HSV PCR before stopping a prolonged course if steroids were used — viral clearance is the open question
• Relapse after apparent recovery warrants re-imaging and repeat PCR rather than assumption of autoimmune encephalitis

Why it matters

A treatment many units give by habit turns out to rest on two small trials that answer neither way.

Don't overread it

This does not show corticosteroids are harmful, and it says nothing about the severe-oedema case where they are most often used.

The statistics, in plain English

A risk ratio of exactly 1.00 with an interval of 0.68 to 1.47 is not a finding of no effect — it is an absence of information. With 209 patients across four studies, the data are compatible with a third fewer bad outcomes or half again as many. That is why the authors call for adequately powered trials rather than declaring the question closed.

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