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Neurological features related to influenza virus in the pediatric population: a 3-year monocentric retrospective study

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Abstract

Influenza virus is generally characterized by fever, myalgia, and respiratory symptoms. Neurological entities have already been described, such as acute necrotizing encephalitis (ANE). We aimed to highlight the non-exceptional nature and explore the clinical spectrum and evolution of neurological features related to influenza virus in children. This monocentric observational study included patients under 18 years old, positive for influenza virus, between January 2017 and April 2019 in a pediatric university hospital. Patients were classified into two groups: those with or without a previous significant neurological or metabolic disorder. Two hundred eighty-nine children were identified with influenza infection. Thirty seven had a neurological manifestation: 14 patients who had previous significant neurological or metabolic disorder and 23 patients with no medical history. We identified several clinical patterns: 22 patients had seizures, 7 behavior disorders, 5 disturbances of consciousness, and 3 motor deficits. Four were diagnosed with a known influenza-associated neurological syndrome: 1 ANE, 1 cytotoxic lesion of the corpus callosum, 1 hemiconvulsion-hemiplegia-epilepsia syndrome, and 1 recurrent encephalitis in the context of a RANBP2 mutation. The neurological outcome was favorable in most cases. None of the patients with previous significant disorder retained sequalae or had a recurrence. Two patients had a fatal outcome, and both had a predisposing disorder.

Conclusion: Various neurological manifestations can be associated with influenza virus. Certain entities led to a poor prognosis, but in most cases, symptoms improved within a few days. The severity of the neurological manifestations correlated with previous neurological or metabolic disorders.

What is Known:

• Influenza viruses are well known pathogens with a seasonal epidemic evolution, particularly affecting children. These viruses cause acute fever with respiratory symptoms, associated with myalgia and headaches. Neurological presentation in influenza‐virus infection is a well‐established possibility as influenza virus is considered to be responsible for 27 to 36% of childhood encephalitis. Some specific and severe entity as acute necrotizing encephalitis, cytotoxic lesion of the corpus callosum, or Hemiconvulsion‐hemiplegia‐epilepsy syndrome are well described.

What is New:

• In a French monocentric cohort of 37 children with influenza‐related neurologic manifestations, the majority of these manifestations, including seizure, drowsiness, motor deficiency, hallucination… are self limiting and do not lead to after‐effects. In rare cases (4/37), they may reveal severe encephalitis requiring rapid and appropriate treatment. Otherwise, comparison of a group of 14 children with underlying neurological or metabolic disorder with a group of 23 children free of any significant disorder show that the severity of the neurological manifestations was largely related to previous neurological or metabolic disorders highlighting the importance of vaccination in this population.

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The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Abbreviations

ANE:

Acute necrotizing encephalitis

CLOCCs:

Cytotoxic lesion of the corpus callosum

HHE:

Hemiconvulsion-hemiplegia-epilepsy syndrome

IAE:

Influenza-associated encephalopathy/encephalitis

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Authors and Affiliations

  1. Pediatric Neurology Department, Necker-Enfants malades Hospital, APHP, Université de Paris Cité, Paris, France

    Violette Goetz, Manoelle Kossorotoff, Isabelle Desguerre & Mélodie Aubart

  2. Pediatric Emergency Department, Necker-Enfants alades Hospital, APHP, Université de Paris Citém, Paris, France

    David-Dawei Yang & François Angoulvant

  3. Virology Laboratory, Necker-Enfants alades Hospital, APHP, Université de Paris Citém, Paris, France

    Hanene Abid

  4. Paediatric Radiology Department, Necker-Enfants malades Hospital, APHP, Université de Paris Cité, Paris, France

    Charles-Joris Roux & Raphael Levy

  5. INSERM, Centre de Recherche des Cordeliers, UMRS 1138, Sorbonne Université, Université de Paris, Paris, France

    François Angoulvant

  6. INSERM U1163 Institut HU Imagine, Laboratory of Human Genetics of Infectious Disease, Paris, France

    Mélodie Aubart

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Contributions

Violette Goetz, Mélodie Aubart, François Angoulvant, and Isabelle Desguerres contributed to the conception and design of the study. Hanene Abid provided the list of children having influenza virus PCR. Violette Goetz collected and assembled data. Violette Goetz, François Angoulvant, and David-Dawei Yang performed the analysis. Charles-Joris Roux and Raphael Levy selected MRI and CTM iconography. All authors contributed to manuscript revision and read and approved the submitted version.

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Correspondence to François Angoulvant or Mélodie Aubart.

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No animal studies are presented in this manuscript. The study was performed using a data warehouse (DrWH®) that has received ethical approval by the French IRB CPP Ile-de-France II (IRB registration number 00001072), registered under reference 2016–06-01. No potentially identifiable human images or data is presented in this study.

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Goetz, V., Yang, DD., Abid, H. et al. Neurological features related to influenza virus in the pediatric population: a 3-year monocentric retrospective study. Eur J Pediatr 182, 2615–2624 (2023). https://doi.org/10.1007/s00431-023-04901-9

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