Influenza-associated neurological complications during 2014–2017 in Taiwan

Chen, Li Wen; Teng, Chao Ku; Tsai, Yi Shan; Wang, Jieh Neng; Tu, Yi Fang; Shen, Ching Fen; Liu, Ching Chuan

doi:10.1016/j.braindev.2018.05.019

“…In addition, younger children more frequently require intensive care support: we reported 4 cases that needed PICU admission for respiratory failure and liver impairment and all of them were children None of our children had been vaccinated for seasonal influenza, consistent with other studies [2,[6][7][8]19]. It is not proven that vaccination has a preventable role against neurological manifestation and a study to demonstrate vaccine effectiveness appears impractical, due to low case numbers.…”

Section: Discussionsupporting

confidence: 84%

“…As regards outcome, 14 patients recovered without sequelae, and only a 2-year-old girl experienced a minimal impairment in fine motor skills at the moment of discharge. Conversely, previous reports have highlighted a high frequency of poor outcomes with deaths and significant neurologic sequelae at discharge in the survivors [2,[6][7][8]19]. In literature, adverse short-term outcomes were associated with specific acute encephalopathy syndromes: the majority of deaths occurred in children with acute necrotizing encephalopathy (ANE) [7].…”

Section: Discussionmentioning

confidence: 99%

Characteristics and Outcome of Influenza-Associated Encephalopathy/Encephalitis Among Children in a Tertiary Pediatric Hospital in Italy, 2017-2019

Mastrolia

¹

,

Rubino

²

,

Resti

³

et al. 2019

Preprint

0

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BACKGROUND: Influenza is the most frequent cause of acute upper respiratory tract infections during winter season. Although rare, neurological manifestations are known to occur during influenza infection and approximatively three-quarters of cases are in children. In this study, we aimed to characterize the burden and clinical spectrum of influenza-associated encephalopathy and encephalitis in children admitted at a tertiary pediatric hospital in Italy over two influenza seasons (2017-2019). METHODS: We retrospectively analyzed clinical, laboratory, instrumental data and outcome of patients discharged with ICD9-CM 487.0 code RESULTS: Fifteen children (13.1% of those discharged with a diagnosis of influenza infection in the study period), had influenza-associated central nervous system (CNS) manifestations. Eight patients (53.3%) were diagnosed as influenza encephalitis, 7 (46.7%) as influenza encephalopathy. Median age was 27 months. In children under 2 years of age (40% of all cases) altered consciousness was the most frequent neurological manifestation while respiratory symptoms were present at admission in all cases. Younger children also required intensive care support more frequently. Five subjects (33.3%) presented comorbidity. None of the patients had received seasonal influenza vaccination. The median time from onset of respiratory signs to onset of neurological manifestations was 24 hours. Cerebrospinal fluid (CSF) analysis was normal in most patients and polymerase chain reaction for influenza virus RNA on CSF, when performed, was negative in all samples. Neuroradiological investigations, performed in 5 children, reported cortical and subcortical white matter signal alterations. Oseltamivir was administered only in 2 cases. Fourteen patients recovered without sequelae, and only a 2-year-old girl had minimal impairment in fine motor skills at discharge. CONCLUSIONS: All children presenting acute neurological features during influenza season should be evaluated for influenza-associated CNS complications even if the respiratory involvement is mild. Absence of underlying diseases or other risk factors are not protective factors against CNS influenza-associated complications. The lack of CSF pleocytosis does not exclude CNS involvement. Children under 2 years of age are at higher risk of requiring intensive care support.

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“…In addition, younger children more frequently require intensive care support: we reported 4 cases that needed PICU admission for respiratory failure and liver impairment and all of them were children None of our children had been vaccinated for seasonal influenza, consistent with other studies [2,[6][7][8]19]. It is not proven that vaccination has a preventable role against neurological manifestation and a study to demonstrate vaccine effectiveness appears impractical, due to low case numbers.…”

Section: Discussionsupporting

confidence: 84%

“…In our study, laboratory data did not show any significant alteration either when the whole study group was observed, or when the cohort was divided into the two different age groups, as reported in available literature [2,[5][6][7][8]19,24].…”

Section: Discussionsupporting

confidence: 69%

“…As regards outcome, 14 patients recovered without sequelae, and only a 2-year-old girl experienced a minimal impairment in fine motor skills at the moment of discharge. Conversely, previous reports have highlighted a high frequency of poor outcomes with deaths and significant neurologic sequelae at discharge in the survivors [2,[6][7][8]19]. In literature, adverse short-term outcomes were associated with specific acute encephalopathy syndromes: the majority of deaths occurred in children with acute necrotizing encephalopathy [7].…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Characteristics And Outcome Of Influenza-Associated Encephalopathy/Encephalitis Among Children In A Tertiary Pediatric Hospital In Italy, 2017-2019

Mastrolia

¹

,

Rubino

²

,

Resti

³

et al. 2019

Preprint

0

View full text Add to dashboard Cite

BACKGROUND: Influenza is the most frequent cause of acute upper respiratory tract infections during winter season. Although rare, neurological manifestations are known to occur during influenza infection and approximatively three-quarters of cases are in children. In this study, we aimed to characterize the burden and clinical spectrum of influenza-associated encephalopathy and encephalitis in children admitted at a tertiary pediatric hospital in Italy over two influenza seasons (2017-2019). METHODS: We retrospectively analyzed clinical, laboratory, instrumental data and outcome of patients discharged with ICD9-CM 487.0 code RESULTS: Fifteen children (13.1% of those discharged with a diagnosis of influenza infection in the study period), had influenza-associated central nervous system (CNS) manifestations. Eight patients (53.3%) were diagnosed as influenza encephalitis, 7 (46.7%) as influenza encephalopathy. Median age was 27 months. In children under 2 years of age (40% of all cases) altered consciousness was the most frequent neurological manifestation while respiratory symptoms were present at admission in all cases. Younger children also required intensive care support more frequently. Five subjects (33.3%) presented comorbidity. None of the patients had received seasonal influenza vaccination. The median time from onset of respiratory signs to onset of neurological manifestations was 24 hours. Cerebrospinal fluid (CSF) analysis was normal in most patients and polymerase chain reaction for influenza virus RNA on CSF, when performed, was negative in all samples. Neuroradiological investigations, performed in 5 children, reported cortical and subcortical white matter signal alterations. Oseltamivir was administered only in 2 cases. Fourteen patients recovered without sequelae, and only a 2-year-old girl had minimal impairment in fine motor skills at discharge. CONCLUSIONS: All children presenting acute neurological features during influenza season should be evaluated for influenza-associated CNS complications even if the respiratory involvement is mild. Absence of underlying diseases or other risk factors are not protective factors against CNS influenza-associated complications. The lack of CSF pleocytosis does not exclude CNS involvement. Children under 2 years of age are at higher risk of requiring intensive care support.

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

Kimura-Ohba,

Kitamura,

Tsukamoto

et al. 2024

Acta Neuropathol

0

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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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Influenza-associated neurological complications during 2014–2017 in Taiwan

Cited by 31 publications

References 19 publications

Characteristics and Outcome of Influenza-Associated Encephalopathy/Encephalitis Among Children in a Tertiary Pediatric Hospital in Italy, 2017-2019

Characteristics and Outcome of Influenza-Associated Encephalopathy/Encephalitis Among Children in a Tertiary Pediatric Hospital in Italy, 2017-2019

Characteristics And Outcome Of Influenza-Associated Encephalopathy/Encephalitis Among Children In A Tertiary Pediatric Hospital In Italy, 2017-2019

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

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