Late delirious behavior with 2009 H1N1 influenza: mild autoimmune-mediated encephalitis?

Delirious behavior associated with influenza usually has an onset within a few days after fever and lasts <24 hours. As we encountered several patients with 2009 H1N1 influenza who presented with late-onset and long-standing delirious behavior, we retrospectively evaluated the clinical, radiologic, and laboratory features to elucidate the possible pathophysiology. This information was collected on 5 previously healthy patients (2 boys and 3 girls, aged 10-15 years) with 2009 H1N1 influenza who presented with late onset (>3 days after fever) and long-standing (>48 hours) delirious behavior. Each exhibited mild to moderate drowsiness between the episodes of delirious behavior. Electroencephalography was normal except for 1 patient with high voltage and slow activity bilaterally in the occipital regions. Brain MRI was normal. The outcome was excellent with no neurologic sequel in 4 of the 5 patients. In all 5 patients, autoantibodies against N-methyl-D-aspartate type glutamate receptor were elevated or positive in cerebrospinal fluid or serum; the autoantibody levels normalized in the 3 patients who had follow-up studies. This study indicates that 2009 H1N1 influenza has a tendency to cause late-onset and long-standing delirious behavior, at least in Japanese children. Mild autoimmune-mediated encephalitis should be considered as an underlying cause.