Acute encephalopathy and encephalitis caused by influenza virus infection

Influenza-associated acute encephalopathy/encephalitis (IAE) is an uncommon but serious complication with high mortality and neurological sequelae. This review discusses recent progress in IAE research for a better understanding of the disease features, populations, outcomes, diagnosis, and pathogenesis.

In recent years, many IAE cases were reported from many countries, including Japan, Canada, Australia, Austria, The Netherlands, United States, Sweden, and other countries and regions. During the novel influenza A/H1N1 pandemic, many IAE cases with A/H1N1 infection in children were reported, particularly in those hospitalized with influenza infection. Pathogenesis of IAE is not fully understood but may involve viral invasion of the CNS, proinflammatory cytokines, metabolic disorders, or genetic susceptibility. An autosomal dominant viral acute necrotizing encephalopathy (ANE) was recently found to have missense mutations in the gene Ran-binding 2 (RANBP2). Another recurrent ANE case following influenza A infection was also reported in a genetically predisposed family with an RANBP2 mutation.

Although IAE is uncommon, compared with the high incidence of influenza infection, it is severe. However, this complication is not duly recognized by health practitioners. Recent advances highlight the threat of this complication, which will help us to have a better understanding of IAE.