Long-term outcomes of childhood encephalitis in Australia: burden and predictors from the Australian childhood encephalitis (ACE) prospective multicentre cohort

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Background: Encephalitis is inflammation of the brain parenchyma with heterogenous aetiology and presentation. In children, it often leads to short-term residual neurological deficits, however clinical predictors of adverse long-term outcome are not fully understood. Methods: Cases of suspected encephalitis, in children aged 0 to <15 years, were actively identified from five paediatric hospitals in Australia, from March 2014 to June 2018. An expert panel categorised them into aetiological subgroups. Follow-up was conducted at discharge and 12 months using the Liverpool outcome score as the primary outcome. Potential clinical predictors of adverse outcome were determined using univariate logistic regression. Findings: Of 724 suspected cases identified, 408 were confirmed as having encephalitis (58% infectious, 23% immune mediated, 19% of unknown aetiology). Recovery was incomplete in 58% of children at 12 months. Children with infectious encephalitis presented younger (median age 1.4 years) and showed divergent trajectories of outcome progression from discharge to 12 months. Immune mediated encephalitis affected mainly older children (median age 7.5 years) and overall showed trajectory to improved neurological outcome at 12 months relative to discharge. Hospital length of stay (OR = 1.02, 95% CI [1.01, 1.03]; p = 0.001), ICU length of stay (OR = 1.07, CI 1.01, 1.13]; p = 0.004), personality/behavioural change >24 h (OR = 1.91, 95% CI [1.01, 3.61]; p = 0.045), motor weakness (OR = 2.05, 95% CI [1.16, 3.64]; p = 0.013), and MRI consistent with encephalitis (OR = 2.22, 95% CI [1.19, 4.13]; p = 0.012), were significantly associated with worse neurological outcomes at 12 months. Interpretation: Encephalitis in children results in a considerable ongoing disease burden with clinical features and outcome differing based on disease aetiology. Neurological deficits may manifest over time and close monitoring of children for at least 12 months is warranted. Funding: National Health and Medical Research Council (NHMRC) centres for research excellence (CRE) in critical infections (APP1001021) to CJ, RB. NHMRC post-graduate scholarship (GNT1074547) and early career fellowship (GNT1145817) to PB.

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