Early vs late diagnosis in infectious encephalitis: a population-based cohort study

To investigate the clinical characteristics and outcomes of patients with early vs. late diagnosis of infectious encephalitis in Denmark.

A nationwide, prospective, population-based cohort study was conducted using the Danish Study Group for Infections of the Brain database to identify all adults hospitalized with infectious encephalitis from 2015 to 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 score <5. Relative risks (RRs) with 95% CIs for receiving a late diagnosis and the associated prognosis were assessed using modified multivariable Poisson regression.

Infectious encephalitis was identified in 495 patients; among these, 183 of 495 (37%) cases were categorized as early diagnosis and 312 of 495 (63%) as late diagnosis. Median time to diagnosis was 12 hours (interquartile range [IQR], 4-43 hours). Patients with late diagnosis were older than those with early diagnosis (72 years [IQR, 61-79 years] vs. 65 years [IQR, 43-75 years]). A late diagnosis was less likely in patients presenting with Glasgow Coma Scale score <12 (adjusted RR, 0.61; 95% CI, 0.42-0.89), varicella zoster virus encephalitis (adjusted RR, 0.69; 95% CI, 0.55-0.86), or an unknown aetiology (adjusted RR, 0. 72; 95% CI, 0.57-0.91). In patients with early diagnosis, 30-day mortality was 8 of 183 (4%) compared with 32 of 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 (adjusted RR, 2.20; 95% CI, 1.16-4.19) and 6 months (adjusted RR, 1.59; 95% CI, 1.06-2.39).

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.