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Influenza virus-induced encephalopathy: clinicopathologic study of an autopsied case
M Takahashi1, T Yamada, Y Nakashita
1Department of Internal Medicine and Health Care, School of Medicine, Fukuoka University, Fukuoka, Japan. takahasi@fukuoka-u.ac.jp
Insights
Influenza A virus can invade the brain, causing severe encephalopathy in children. Rapid blood-brain barrier breakdown and cytokine release, not just direct viral damage, likely drive this rapid, severe neurological disease.
Area of Science:
- Neurology
- Virology
- Pathology
Background:
- Hemorrhagic shock and encephalopathy syndrome (HSES) is a severe neurological condition occasionally reported in children during influenza pandemics in Japan.
- The exact pathogenesis of HSES, particularly the role of direct viral invasion versus host immune response, remains unclear due to limited histologic and virologic data.
Observation:
- A clinicopathologic study was conducted on a 2-year-old girl with HSES associated with acute influenza A virus (H3N2) infection.
- Immunohistochemical staining and RT-PCR were used to analyze autopsy tissues and cerebrospinal fluid.
Findings:
- Influenza A virus antigens were detected in CD8+ T lymphocytes in the lung and spleen.
- The virus infected limited brain regions, including Purkinje cells and pons neurons, with minimal host immune reaction observed in the brain.
- Viral RNA was detected in autopsy tissues and cerebrospinal fluid, but not in samples taken during initial admission.
Implications:
- Direct viral invasion alone may not explain the rapid and severe clinical course of HSES.
- Breakdown of the blood-brain barrier, coupled with rapid inflammatory cytokine production, likely contributes significantly to severe brain edema and the disease's progression.
- Therapeutic strategies targeting this multistep disease progression may offer effective treatment options for HSES.
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.