CSF neopterin, a useful biomarker in children presenting with influenza associated encephalopathy?

Eur J Paediatr Neurol. 2019 Jan;23(1):204-213. doi: 10.1016/j.ejpn.2018.09.009. Epub 2018 Sep 28.


Purpose: Neurological complications of influenza cause significant disease in children. Central nervous system inflammation, the presumed mechanism of influenza-associated encephalopathy, is difficult to detect. Characteristics of children presenting with severe neurological complications of influenza, and potential biomarkers of influenza-associated encephalopathy are described.

Methods: A multi-center, retrospective case-series of children with influenza and neurological complications during 2017 was performed. Enrolled cases met criteria for influenza-associated encephalopathy or had status epilepticus. Functional outcome at discharge was compared between groups using the Modified Rankin Scale (mRS).

Results: There were 22 children with influenza studied of whom 11/22 had encephalopathy and 11/22 had status epilepticus. Only one child had a documented influenza immunization. The biomarker CSF neopterin was tested in 10/11 children with encephalopathy and was elevated in 8/10. MRI was performed in all children with encephalopathy and was abnormal in 8 (73%). Treatment of children with encephalopathy was with corticosteroids or intravenous immunoglobulin in 9/11 (82%). In all cases oseltamivir use was low (59%) while admission to the intensive care unit was frequent (14/22, 66%). Clinical outcome at discharge was moderate to severe disability (mRS score > 2) in the majority of children with encephalopathy (7/11, 64%), including one child who died. Children with status epilepticus recovered to near-baseline function in all cases.

Conclusion: Raised CSF neopterin was present in most cases of encephalopathy, and along with diffusion restriction on MRI, is a useful diagnostic biomarker. Lack of seasonal influenza vaccination represents a missed opportunity to prevent illness in children, including severe neurological disease.

Keywords: Encephalitis; Influenza; Influenza-associated encephalitis; Magnetic resonance imaging; Neopterin; Neuroinflammation; Status epilepticus.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Biomarkers / cerebrospinal fluid*
  • Brain Diseases / cerebrospinal fluid*
  • Brain Diseases / diagnosis
  • Brain Diseases / virology*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Influenza, Human / complications*
  • Magnetic Resonance Imaging
  • Male
  • Neopterin / cerebrospinal fluid*
  • Retrospective Studies


  • Biomarkers
  • Neopterin