Early versus late diagnosis in infectious encephalitis: A population-based cohort study

Abstract Objectives To investigate the clinical characteristics and outcomes of patients with early versus late diagnosis of infectious encephalitis in Denmark. Methods Nationwide, prospective, population-based cohort study using the Danish Study Group for Infections of the Brain database to identify all adults hospitalized with infectious encephalitis from 2015-2023. Late diagnosis was defined as lumbar puncture or initiation of acyclovir treatment >6 hours after admission, and very late diagnosis >24 hours after admission. Unfavourable outcome was defined as Glasgow Outcome Scale<5. Relative risks (RR) with 95% confidence intervals (CI) for receiving a late diagnosis and the associated prognosis were assessed using modified multivariable Poisson regression. Results Infectious encephalitis was identified in 495 patients of whom 183/495 (37%) were categorized as early diagnosis and 312/495 (63%) as late diagnosis. Median time to diagnosis was 12 hours (interquartile range [IQR] 4-43). Patients with late diagnosis were older compared to those with early diagnosis (72 years, IQR 61-79 vs 65 years, IQR 43-75). A late diagnosis was less likely in patients presenting with GCS <12 (Adj. RR 0.61; 95%CI 0.42–0.89), VZV encephalitis (Adj. RR 0.69, 95%CI 0.55-0.86), or an unknown aetiology (Adj. RR 0. 72, 95%CI 0.57-0.91). In patients with early diagnosis, 30-day mortality was 8/183 (4%) compared with 32/312 (10%) in patients with late diagnosis. Multivariable analysis showed no association between late diagnosis and unfavourable outcome at 6-months. However, diagnosis >24 hours after admission was associated with increased mortality at 30 days (Adj. RR 2.20; 95% CI 1.16-4.19) and six months (Adj. RR 1.59 95%CI 1.06-2.39). Conclusion Late diagnosis of infectious encephalitis remains common and is associated with older age and absence of altered mental status at admission. Receiving a diagnosis >24 hours after admission is associated with increased risk of 30-day and 6-month mortality.