National survey of pandemic influenza A (H1N1) 2009-associated encephalopathy in Japanese children



The novel pandemic (pdm) influenza A (H1N1) 2009 virus caused an epidemic of critical illness, with some patients developing severe acute respiratory distress syndrome. Pdm H1N1 2009 infection has been reported to cause fatal encephalopathy and myocarditis as well as pneumonia. To investigate the actual characteristics of the encephalopathy associated with pdm H1N1 2009 infection in Japan, questionnaires were distributed and information collected on 207 cases of encephalopathy during one season. The results of the survey showed that encephalopathy was reported predominantly in males. The outcome was recorded in 188 of the 207 cases; 16 of 188 patients (8.5%) died, while 23 (12.2%) had sequelae. Serious cases were distributed across all age groups. Febrile convulsion was noted at a higher rate in medical past-history in cases without sequelae (40 of the 149 cases; 27%) than in serious cases. In contrast, pre-existing epilepsy and mental retardation were observed more frequently in serious cases. Twelve cases exhibited biphasic seizures; one-half of these had sequelae, but none was fatal. Ten cases were accompanied by high cytokine levels, and three of these children died. Among the 149 cases with good outcomes, 29 of 116 cases (25%) showed abnormalities on MRI, and 14 of these demonstrated reversible splenial lesions. Abnormal behaviors, especially delirium and visual hallucinations, were observed more frequently in cases without sequelae. In conclusion, pdm H1N1 2009 infection-associated encephalopathy was a critical disease in children, with rapidly progressive characteristics similar to those of seasonal influenza-associated encephalopathy. J. Med. Virol. 84: 1151–1156, 2012. © 2012 Wiley Periodicals, Inc.