Lærke Storgaard Duerlund, Lykke Larsen, Merete Storgaard, Helene Mens, Lothar Wiese, Micha Phill Grønholm Jepsen, Birgitte Rønde Hansen, Hans Rudolf Lüttichau, Christian Østergaard Andersen, Morten Blaabjerg, Arun Venkatesan, Henrik Nielsen, Jacob Bodilsen, the DASGIB study group, Lykke Larsen, Merete Storgaard, Helene Mens, Lothar Wiese, Micha Phill Grønholm Jepsen, Birgitte Rønde Hansen, Hans Rudolf Lüttichau, Christian Østergaard Andersen, Henrik Nielsen, Jacob Bodilsen
BACKGROUND: This study was performed to investigate the clinical characteristics and outcome of patients with herpes simplex (HSV) type 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 to 2023 in Denmark. Modified Poisson regression was used to estimate the relative risk (RR) with 95% confidence intervals (CI) for 6-month mortality, adjusted for age, sex, immunocompromise, altered mental status, imaging abnormalities, time to acyclovir (>6 hours from admission), and pathogen. Analysis of acyclovir delay >6 hours was repeated post-hoc using time after lumbar puncture as reference. RESULTS: A total of 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 (in 101/128 [79%]) and confusion (in 99/154 [78%]). The median times from admission to lumbar puncture and acyclovir treatment were 21 (interquartile range, 6-70) and 24 (7-74) hours, 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. CONCLUSIONS: 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.