Related Experiment Videos
Influenza-associated encephalopathy in Japan: pathogenesis and treatment
1Department of Pediatrics, Nippon Kokan Hospital, Kanagawa, Japan. sugaya-n@za2.so-net.ne.jp
Insights
Influenza encephalopathy causes over 100 child deaths annually in Japan. A specific influenza A (H3N2) virus variant may be responsible, potentially linked to cytokine activity.
Area of Science:
- Neurology
- Virology
- Immunology
Background:
- Influenza-associated encephalopathy (IAE) is a severe neurological complication of influenza, distinct from Reye's syndrome.
- IAE leads to over 100 pediatric deaths yearly in Japan, highlighting its significant public health impact.
Observation:
- A subset of IAE patients (20%) shows bilateral thalamic necrosis, termed acute necrotizing encephalopathy (ANE).
- IAE pathogenesis may involve CNS vasoconstriction or vasoactive substances, similar to ANE.
- A specific mutation (Tyr137Phe) in influenza A (H3N2) viruses has been exclusively found in IAE patients.
Findings:
- The identified influenza A (H3N2) variant suggests a potential viral cause for encephalopathy.
- Elevated plasma interleukin-6 levels may indicate disease progression in IAE.
- Cytokines are implicated as potential mediators in the pathogenesis of influenza encephalopathy.
Implications:
- Understanding the specific viral variant and cytokine involvement could lead to targeted therapies for IAE.
- Further research is needed to determine if the influenza virus invades the central nervous system.
- Amantadine therapy has been explored in Japan for influenza A-positive IAE cases.
Abstract:
It is estimated that more than 100 children die of influenza-associated encephalopathy (influenza encephalopathy) every year in Japan. Influenza encephalopathy is distinct from Reye's syndrome. Specifically, 20% of influenza encephalopathy patients exhibit bilateral thalamic necrosis on neuroimaging, a lesion referred to as acute necrotizing encephalopathy (ANE). Influenza encephalopathy may develop by the same pathogenetic mechanisms as ANE, possibly via vasoactive substances or a process leading to vasoconstriction in the central nervous system (CNS). A novel substitution at the receptor-binding site (Tyr 137 to Phe) was reported to be found exclusively in influenza type A (H3N2) viruses isolated from patients with influenza encephalopathy, suggesting that encephalopathy may be caused by a variant influenza type A (H3N2) virus. Recently, it has been reported that cytokines may mediate the disease and that a high plasma concentration of interleukin-6 could be an indicator of progression to encephalopathy. Although it is unknown whether influenza virus invades the CNS, amantadine therapy for influenza encephalopathy has been tried in Japan, in patients in whom influenza type A infection has been demonstrated by rapid antigen detection tests.