Respiratory Syncytial Virus–Associated Neurologic Complications in Children: A Systematic Review and Aggregated Case Series

Saravanos, Gemma L; King, Catherine; Deng, Lucy; Dinsmore, Nicole; Ramos, Isabelle; Takashima, Mari; Crawford, Nigel; Clark, Julia; Dale, Russell C.; Jones, Cheryl; Wood, Nicholas; Britton, Philip N

doi:10.1016/j.jpeds.2021.06.045

Cited by 24 publications

(25 citation statements)

References 89 publications

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“…The potential causes among cases described here including respiratory viruses (influenza A, respiratory syncytial virus B, parainfluenza, bocavirus, and human metapneumovirus), enteroviruses, and M pneumoniae overlap substantially with the causes of childhood encephalitis and infection-associated encephalopathies and may inform future studies of aetiology. 9,18,19…”

Section: Discussionmentioning

confidence: 99%

Postinfectious Acute Cerebellar Syndromes in Children: A Nationally Ascertained Case Series From Australia 2013–2018

et al. 2022

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Introduction Postinfectious acute cerebellar syndromes show a wide spectrum of acute severity and can occur with acute febrile illness or vaccine receipt. Varicella has historically been the most common cause, associated with up to 25% of cases in large cohorts. This study aimed to describe the spectrum of syndromes in a setting with high varicella vaccine coverage. Method Data were collected on children initially identified as “suspected encephalitis” subsequently designated “not-encephalitis” at participating children's hospitals in the Paediatric Active Enhanced Disease Surveillance (PAEDS) network, Australia, as part of the Acute Childhood Encephalitis study. A comprehensive descriptive analysis was undertaken on prospectively identified, national series of children with postinfectious acute cerebellar syndromes from 2013 to 2018. Cases were classified using a previously validated severity score, and the outcome was assessed at 12 months using the Liverpool Outcome Scale score. Results A total of 20 cases (65% were vaccinated for varicella) were included, of which 70% were subcategorized as acute cerebellar ataxia (ACA), 20% acute cerebellitis (AC), and 10% acute fulminant cerebellitis (AFC). An acute febrile illness was noted in 55% and none were related to varicella or were temporally related to varicella vaccination or other childhood vaccines. A subset (total of 7 children) followed up at 12 months all showed reduced Liverpool Outcome Scale scores. Discussion The study provides an overall description of this uncommon spectrum of neurologic syndromes and shows the infrequency of varicella zoster virus as a cause in a vaccinated population.

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Section: Discussionmentioning

confidence: 99%

Postinfectious Acute Cerebellar Syndromes in Children: A Nationally Ascertained Case Series From Australia 2013–2018

et al. 2022

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“…Among these patients with neurological symptoms, the genetic material of hRSV was found on the cerebrospinal fluid (CSF) and presented elevated cytokines [82,83]. The percentage of acute encephalitis or encephalopathy cases in infants due to the infection with hRSV can reach up to 6.5% [84]. Unfortunately, not all children can recover entirely from the neurological symptoms, and even 7% of the cases result in the death of the patient [84].…”

Section: Neurological Consequences Due To Hrsv Infectionmentioning

confidence: 99%

“…The percentage of acute encephalitis or encephalopathy cases in infants due to the infection with hRSV can reach up to 6.5% [84]. Unfortunately, not all children can recover entirely from the neurological symptoms, and even 7% of the cases result in the death of the patient [84]. Recently, a rare manifestation that contributes to neurological symptoms due to the infection with hRSV was reported [85].…”

Section: Neurological Consequences Due To Hrsv Infectionmentioning

confidence: 99%

Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

2021

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Respiratory infections are among the major public health burdens, especially during winter. Along these lines, the human respiratory syncytial virus (hRSV) is the principal viral agent causing acute lower respiratory tract infections leading to hospitalization. The pulmonary manifestations due to hRSV infection are bronchiolitis and pneumonia, where the population most affected are infants and the elderly. However, recent evidence suggests that hRSV infection can impact the mother and fetus during pregnancy. Studies have indicated that hRSV can infect different cell types from the placenta and even cross the placenta barrier and infect the fetus. In addition, it is known that infections during the gestational period can lead to severe consequences for the development of the fetus due not only to a direct viral infection but also because of maternal immune activation (MIA). Furthermore, it has been described that the development of the central nervous system (CNS) of the fetus can be affected by the inflammatory environment of the uterus caused by viral infections. Increasing evidence supports the notion that hRSV could invade the CNS and infect nervous cells, such as microglia, neurons, and astrocytes, promoting neuroinflammation. Moreover, it has been described that the hRSV infection can provoke neurological manifestations, including cognitive impairment and behavioral alterations. Here, we will review the potential effect of hRSV in brain development and the potential long-term neurological sequelae.

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“…Clinically, diffusion-weighted magnetic resonance imaging (DWI) show that greater migration of neutrophils to the ischemic hemisphere can result in larger infarct volumes in the acute phase after stroke ( Buck et al., 2008 ). As RSV infection can cause neurological consequences in patients, such as communicative disabilities and seizure ( Peña et al., 2020 ; Saravanos et al., 2021 ), our results indicate that neutrophils may play a vital role in the neurological complications caused by RSV infection. Notably, the “factors involved in megakaryocyte development and platelet production” pathway was specifically enriched in the lung, which may explain platelet elevation post-RSV infection ( Zheng et al., 2016 ).…”

Section: Discussionmentioning

confidence: 71%

“…Complications caused by RSV infection have been observed and reported in many clinical studies. These complications can increase the risk of death and prolong hospital stays, and involve respiratory failure ( Geoghegan et al., 2017 ; Kong et al., 2020 ), acute respiratory distress syndrome ( Dahlem et al., 2007 ; Subissi et al., 2020 ), and pneumorrhagia ( Soo and Inwald, 2017 ), as well as a spectrum of neurological complications, such as encephalitis, acute encephalopathy, complex seizures, hyponatremic seizures, and immune-mediated disorders with seizure ( Saravanos et al., 2021 ). Digestive system complications, such as diarrhea ( Liu et al., 2016 ), and hematological complications, such as secondary thrombocytosis and anemia ( Zheng et al., 2016 ), have also been reported.…”

Section: Introductionmentioning

confidence: 99%

Exploring Key Genes and Mechanisms in Respiratory Syncytial Virus-Infected BALB/c Mice via Multi-Organ Expression Profiles

Wang

Wei

et al. 2022

Front. Cell. Infect. Microbiol.

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Respiratory syncytial virus (RSV) a leading cause of pediatric and adult morbidity and mortality worldwide. It can cause complications in multiple organs, thus increasing hospital stays and costs. However, RSV-based studies have primarily focused on effects in the lungs and blood, thereby potentially neglecting critical genes and pathways. Hence, studying RSV infection via a novel multi-organ approach is important. In this study, lung, intestine, brain, and spleen tissues from six BALB/c mice (6–8 weeks old; three in control group and three in RSV-infected group) were subjected to RNA sequencing. Differentially expressed genes (DEGs) in each organ were obtained and functional enrichment analysis was performed. We first used CIBERSORT to evaluate the immune-infiltration landscape. Subsequently, common DEGs (co-DEGs) among the four organs were analyzed to identify key genes and pathways. After quantitative reverse transcription-polymerase chain reaction, western blotting, and external validation analysis of key hub genes, their correlation with immune cells and potential functions were explored. We found that the host response to RSV infection varied among the four organs regarding gene expression profiles and immune cell infiltration. Analysis of the 16 co-DEGs indicated enrichment in the platelet and neutrophil degranulation pathways. Importantly, the key gene hemopexin (Hpx) was strongly correlated with the immune cell fraction in the lungs and may participate in the regulation of platelet activation and immune response.

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Respiratory Syncytial Virus–Associated Neurologic Complications in Children: A Systematic Review and Aggregated Case Series

Cited by 24 publications

References 89 publications

Postinfectious Acute Cerebellar Syndromes in Children: A Nationally Ascertained Case Series From Australia 2013–2018

Postinfectious Acute Cerebellar Syndromes in Children: A Nationally Ascertained Case Series From Australia 2013–2018

Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

Exploring Key Genes and Mechanisms in Respiratory Syncytial Virus-Infected BALB/c Mice via Multi-Organ Expression Profiles

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