A sudden death due to acute necrotizing encephalopathy associated with influenza A virus infection: An autopsy case report

Huang, Weijian; Zhou, Hui; Wu, Shuang; Gao, Qing; Sun, Tianying; Yang, Chenguang; Dong, Hongmei

doi:10.1016/j.legalmed.2022.102098

Cited by 5 publications

(4 citation statements)

References 17 publications

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“…In the present study, we detected live virus and viral RNA in the IVE mouse brains and viral protein accumulation in the brains of both the IVE mice and IAE patients. Previous studies have also reported the viral detection from neurons, EC, astrocytes, and CD8-positive cells in IAE autopsy brains [ 19 , 23 , 37 , 88 , 99 ]. The routes to the extra-respiratory organs, especially central nervous system (CNS), of influenza virus invasion has long been a debate [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…The inflammatory response is inactive, while multiple vascular lesions, such as hemorrhage, bleedings, fibrin thrombosis, and leakage of plasma components, are observed in the brain parenchyma [ 44 , 49 , 67 ]. It is noteworthy that the virus antigen was detected in some cases in the brain parenchyma and spinal fluid [ 19 , 23 , 88 , 99 ]. The detection of viral antigen or RNA from edematous brains has been also reported with the influenza virus-inoculated mouse models [ 80 , 101 ].…”

Section: Introductionmentioning

confidence: 99%

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Viral entry and translation in brain endothelia provoke influenza-associated encephalopathy

Kimura-Ohba,

Kitamura,

Tsukamoto

et al. 2024

Acta Neuropathol

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Influenza-associated encephalopathy (IAE) is extremely acute in onset, with high lethality and morbidity within a few days, while the direct pathogenesis by influenza virus in this acute phase in the brain is largely unknown. Here we show that influenza virus enters into the cerebral endothelium and thereby induces IAE. Three-weeks-old young mice were inoculated with influenza A virus (IAV). Physical and neurological scores were recorded and temporal-spatial analyses of histopathology and viral studies were performed up to 72 h post inoculation. Histopathological examinations were also performed using IAE human autopsy brains. Viral infection, proliferation and pathogenesis were analyzed in cell lines of endothelium and astrocyte. The effects of anti-influenza viral drugs were tested in the cell lines and animal models. Upon intravenous inoculation of IAV in mice, the mice developed encephalopathy with brain edema and pathological lesions represented by micro bleeding and injured astrocytic process (clasmatodendrosis) within 72 h. Histologically, massive deposits of viral nucleoprotein were observed as early as 24 h post infection in the brain endothelial cells of mouse models and the IAE patients. IAV inoculated endothelial cell lines showed deposition of viral proteins and provoked cell death, while IAV scarcely amplified. Inhibition of viral transcription and translation suppressed the endothelial cell death and the lethality of mouse models. These data suggest that the onset of encephalopathy should be induced by cerebral endothelial infection with IAV. Thus, IAV entry into the endothelium, and transcription and/or translation of viral RNA, but not viral proliferation, should be the key pathogenesis of IAE.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Viral entry and translation in brain endothelia provoke influenza-associated encephalopathy

Kimura-Ohba,

Kitamura,

Tsukamoto

et al. 2024

Acta Neuropathol

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“…Ikeda et al [45] proposed that RSV immunopositivity is located in the bronchial epithelium and intra-alveolar cells, which helps to determine the cause of deaths related to RSV infection. In our previous study, we presented a rare case of acute necrotizing encephalopathy based on the influenza A virus NS1 immunopositive located in the main organs (including bilateral thalamus and pons, epithelium of the larynx, and the pulmonary alveoli) [46].…”

Section: Immunohistochemistry (Ihc) Assaymentioning

confidence: 99%

The Role of Protein Degradation in Estimation Postmortem Interval and Confirmation of Cause of Death in Forensic Pathology: A Literature Review

Huang,

Zhao,

Liu

et al. 2024

IJMS

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It is well known that proteins are important bio-macromolecules in human organisms, and numerous proteins are widely used in the clinical practice, whereas their application in forensic science is currently limited. This limitation is mainly attributed to the postmortem degradation of targeted proteins, which can significantly impact final conclusions. In the last decade, numerous methods have been established to detect the protein from a forensic perspective, and some of the postmortem proteins have been applied in forensic practice. To better understand the emerging issues and challenges in postmortem proteins, we have reviewed the current application of protein technologies at postmortem in forensic practice. Meanwhile, we discuss the application of proteins in identifying the cause of death, and postmortem interval (PMI). Finally, we highlight the interpretability and limitations of postmortem protein challenges. We believe that utilizing the multi-omics method can enhance the comprehensiveness of applying proteins in forensic practice.

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“…Acute necrotizing encephalopathy (ANE) is a rare, rapidly progressive, post-infection acute severe encephalopathy named after its clinicopathological features. It has a poor prognosis and a high mortality rate, with approximately three-quarters of cases associated with children, resulting in a mortality rate of up to 30% ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

Risk factors for death associated with severe influenza in children and the impact of the COVID-19 pandemic on clinical characteristics

Hu,

Liang,

et al. 2023

Front. Pediatr.

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BackgroundTo summarize the clinical features of severe influenza in children and the high-risk factors for influenza-related deaths and to raise awareness among pediatricians.MethodsA retrospective study of clinical manifestations, laboratory tests, and diagnosis and treatment of 243 children with severe influenza admitted to Shenzhen Children's Hospital from January 2009 to December 2022 was conducted. Univariate logistic regression analysis and Boruta analysis were also performed to identify potentially critical clinical characteristics associated with death, and clinically significant were used in further multivariate logistic regression analysis. Subject receiver operating characteristic (ROC) curves were applied to assess the efficacy of death-related independent risk factors to predict death from severe influenza.ResultsThere were 169 male and 74 female patients with severe influenza, with a median age of 3 years and 2 months and 77.4% of patients under six. There were 46 cases (18.9%) in the death group. The most common pathogen was Influenza A virus (IAV) (81.5%). The most common complication in the death group was influenza-associated acute necrotizing encephalopathy (ANE [52.2%]). Severe influenza in children decreased significantly during the COVID-19 pandemic, with a median age of 5 years, a high predominance of neurological symptoms such as ANE (P = 0.001), and the most common pathogen being H3N2 (P < 0.001). D-dimer, acute respiratory distress syndrome (ARDS), and acute necrotizing encephalopathy (ANE) were significant independent risk factors for severe influenza-associated death. Furthermore, the ROC curves showed that the combined diagnosis of independent risk factors had significant early diagnostic value for severe influenza-related deaths.ConclusionNeurological disorders such as ANE are more significant in children with severe influenza after the COVID-19 pandemic. Influenza virus infection can cause serious multisystem complications such as ARDS and ANE, and D-dimer has predictive value for early diagnosis and determination of the prognosis of children with severe influenza.

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A sudden death due to acute necrotizing encephalopathy associated with influenza A virus infection: An autopsy case report

Cited by 5 publications

References 17 publications

Viral entry and translation in brain endothelia provoke influenza-associated encephalopathy

Viral entry and translation in brain endothelia provoke influenza-associated encephalopathy

The Role of Protein Degradation in Estimation Postmortem Interval and Confirmation of Cause of Death in Forensic Pathology: A Literature Review

Risk factors for death associated with severe influenza in children and the impact of the COVID-19 pandemic on clinical characteristics

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