Infectious encephalitis among adults: a prospective and population-based cohort study

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OBJECTIVES: To examine the incidence, clinical presentation, and prognosis of infectious encephalitis among adults in Denmark. METHODS: Prospective, population-based cohort study using the Danish Study group for Infections of the Brain database to identify all Danish residents ≥18 years of age hospitalized with infectious encephalitis from 2015 to 2023. Cases were defined in alignment with the International Encephalitis Consortium criteria. Multivariable modified Poisson regression was used to compute adjusted relative risks (adj. RRs) with 95% CIs for intensive care unit admission and 6-month mortality. Continuous variables were modelled using restricted cubic splines. Multicollinearity between variables was not found. RESULTS: A total of 495 patients were included yielding an annual mean incidence of 1.18 per 100 000 (95% CI 1.01-1.35). The median age was 70 years (interquartile range 54-78 years) and 240 of 495 (48%) were female. The aetiology comprised Varicella zoster virus in 156 of 495 (32%), Herpes simplex virus type 1 (HSV-1) in 154 of 495 (31%), tick-borne encephalitis in 23 of 495 (5%), other viruses in 40 of 495 (8%), and remained unknown in 122 of 495 (24%). Common symptoms at admission included confusion 391 of 488 (80%), headache 234 of 397 (59%), and personality changes 183 of 439 (42%). Intensive care unit admission occurred in 111 of 495 (22%) and was associated with Glasgow Coma Scale (GCS) <12 (adj. RR 2.52 95% CI 1.58-4.02) and seizures (adj. RR 2.17 95% CI 1.52-3.09). All-cause mortality at 30 days was 41 of 495 (8%) and increased to 76 of 495 (15%) after 6 months. Risk of 6-month mortality was higher in patients with immunocompromise (adj. RR 2.91, 95% CI 1.97-4.31), HSV-1 encephalitis (adj. RR 2.34, 95% CI 1.17-4.72), and GCS <12 (adj. RR 2.03, 95% CI 1.01-4.11). CONCLUSIONS: Infectious encephalitis remains rare with HSV-1 and Varicella zoster virus as common causes. The clinical presentation is unspecific, and the diagnosis remains challenging. Poor outcome is frequent throughout a prolonged follow-up, especially in those with immunocompromising conditions, HSV-1 encephalitis, or a low GCS at admission.

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