Influenza virus‐induced encephalopathy: Clinicopathologic study of an autopsied case

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Abstract
Background : Rapid progressive encephalopathy with a high fever, consciousness loss and recurrent convulsions has been occasionally reported in children during influenza pandemics in Japan since 1995. We examined a 2‐year old girl with hemorrhagic shock and encephalopathy syndrome associated with acute influenza A virus infection (A/Nagasaki/76/98; H3N2), to answer several questions for which no histologic or virologic data exist. Methods : A clinicopathologic study using immunohistochemical staining and viral genome detection by reverse transcriptase polymerase chain reaction (RT‐PCR) was performed with this autopsied case. Results : The virus antigen was positive in CD8+ T lymphocytes from the lung and spleen. The virus infected a very limited part of the brain, especially Purkinje cells in the cerebellum and many neurons in the pons, without inducing an overt immunologic reaction from the host. The RT‐PCR used for detecting the hemagglutinin gene demonstrated positive bands in all frozen tissues and cerebrospinal fluid taken at autopsy and not in samples obtained on admission. Conclusions : The pathologic change induced by the direct viral invasion cannot be responsible for all of the symptoms, especially for the rapid and severe clinical course of the disease within 24–48 h after the initial respiratory symptoms. Together with the rapid production of several inflammatory cytokines, the breakdown of the blood–brain barrier may induce severe brain edema and can be a major pathologic change for the disease. Any therapeutic strategy to control this multistep progression of the disease could be effective.