Abstract Background To investigate the clinical characteristics and outcome of patients with herpes simplex type 1 (HSV-1) encephalitis. Methods Nationwide, prospective, population-based cohort study using the Danish Study Group for Infections of the Brain database to identify all adults hospitalized with microbiologically confirmed HSV-1 encephalitis from 2015-2023 in Denmark. Modified Poisson regression was used to estimate relative risks (RR) with 95% confidence intervals (CI) for 6-month mortality by time to acyclovir after admission and adjusted for age, sex, immunocompromise, altered mental status, and imaging abnormalities. Analysis was repeated post-hoc using time after lumbar puncture as reference. Results Overall, 154 patients with confirmed HSV-1 encephalitis were included yielding a mean annual incidence of 0.36/100.000. Frequent symptoms at admission included a history of fever 101/128 (79%) and confusion 99/154 (78%). The median times from admission to lumbar puncture and acyclovir treatment were 21 hours (interquartile range IQR 6–70) and 24 hours (IQR 7-74), respectively. The adjusted RR for 6-month mortality was 1.15 (95% CI 0.39-3.41) for acyclovir initiation 6 hours after admission and 1.06 (95% CI: 1.004–1.13) for each day of delay after admission. The adjusted RR of 6-month mortality was 1.85 (95% CI: 1.01–3.45) for delayed acyclovir treatment of 6 hours since lumbar puncture. Anti N-Methyl-D-aspartate receptor encephalitis was diagnosed in 9/154 (6%) of patients after HSV-1 encephalitis. Conclusion Early recognition of HSV-1 encephalitis remains challenging, and the condition is associated with high mortality. Delayed acyclovir treatment, especially following lumbar puncture, was associated with increased risks of fatal outcome.
Duerlund et al. (Sun,) studied this question.