Long-term outcomes of infective encephalitis in children: a systematic review and meta-analysis

AIM: The long-term outcomes of childhood infective encephalitis are variable and not well quantified. We aimed to systematically review the literature and undertake meta-analyses on predetermined outcomes to address this knowledge gap and identify areas for future research. METHOD: We searched electronic databases, performed complementary reviews of references of fully extracted articles, and made contact with experts on infective encephalitis. Articles published up until April 2016 were selected for screening. RESULTS: We evaluated sequelae of 1018 survivors of childhood infective encephalitis (934 with complete follow-up) from 16 studies. Mean age during acute encephalitis episodes was 5 years 3.6 months (range 1.2mo-17y), 57.6% were male (500/868), and mean follow-up period was 4 years 1.2 months (range 1-12y). Incomplete recovery was reported in 312 children (42.0%; 95% confidence interval [CI] 31.6-53.1% in pooled estimate). Among the other sequelae, developmental delay, abnormal behaviour, motor impairment, and seizures were reported among 35.0% (95% CI 10.0-65.0%), 18.0% (95% CI 8.0-31.0%), 17.0% (95% CI 10.0-26.0%), and 10.0% (95% CI 6.0-14.0%) respectively. INTERPRETATION: Almost half of childhood infective encephalitis survivors report incomplete recovery in the long-term; most commonly developmental delay, behavioural abnormality, and neurological impairments (i.e. seizure). Well designed, large-scale prospective studies are needed to better quantify neurodevelopmental sequelae among childhood encephalitis survivors.