Neurological manifestations and outcomes of children with the 2009 H1N1 virus infection have been reported in three American series and from smaller cohorts and case reports worldwide. Of the 83 children admitted between April 2009 and March 2010 with H1N1 virus infection to a tertiary children’s hospital in a European setting, five children aged between 2 and 10 years had neurological symptoms. Four patients had seizures and encephalopathy at presentation. One patient presented with ataxia; one developed neuropsychiatric manifestations, and two developed movement disorders during the disease course. Early neuroimaging showed evidence of acute necrotising encephalopathy (ANE) in one case and non-specific white matter changes in another. Initial neuroimaging was normal for the other three, but interval MRI showed increased signal in bilateral periventricular distribution in one and significant cerebral volume loss in the other. Clinical outcomes varied: two recovered fully while three had residual seizures and/or significant cognitive deficits. Conclusion An analysis of our patients along with all reported cases reveal that seizures and encephalopathy were common neurological presentations associated with pandemic 2009 H1N1 influenza virus infection in children requiring hospital admission. Neuroimaging suggestive of ANE, basal ganglia involvement and volume loss appears to be associated with worse neurological outcome.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Acevedo KLM, Ponce S, Cabezas A (2010) Influenza A H1N1 encephalitis: case report [abstract]. Dev Med Child Neurol 52(Suppl 1):P32
Baltagi SA, Shoykhet M, Felmet K et al (2010) Neurological sequelae of 2009 influenza A (H1N1) in children: a case series observed during a pandemic. Pediatr Crit Care Med 11(2):179–184
Belay ED, Bresee JS, Holman RC et al (1999) Reye’s syndrome in the United States from 1981 through 1997. N Engl J Med 340(18):1377–1382
Chiu SS, Tse CY, Lau YL et al (2001) Influenza A infection is an important cause of febrile seizures. Pediatrics 108(4):E63
Choi SY, Jang SH, Kim JO et al (2010) Novel swine-origin influenza A (H1N1) viral encephalitis. Yonsei Med J 51(2):291–292
Cooper NJ, Sutton AJ, Abrams KR et al (2003) Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials. BMJ 326(7401):1235
Ekstrand JJ, Herbener A, Rawlings J et al (2010) Heightened neurologic complications in children with pandemic H1N1 influenza. Ann Neurol Sep 23 doi:10.1002/ana.22184
Evans AS, Agadi S, Siegel SD et al (2009) Neuroloigcal complications associated with novel influenza A (H1N1) virus in children—Dallas, Texas, May 2009. MMWR: Morbidity and Mortality weekly. 24 July 58(28):773–778
Flewett TH, Hoult J (1958) Influenzal encephalopathy and postinfluenzal encephalitis. Lancet 2(7036):11–15
Fujimoto S, Kobayashi M, Uemura O et al (1998) PCR on cerebrospinal fluid to show influenza-associated acute encephalopathy or encephalitis. Lancet 352(9131):873–875
German-Diaz M, Pavo-Garcia R, Diaz-Diaz J et al (2010) Adolescent with neuropsychiatric symptoms associated with novel influenza A (H1N1) virus infection. Pediatr Infect Dis J 29(6):570–571
Glaser CA, Gilliam S, Schnurr D et al (2003) In search of encephalitis etiologies: diagnostic challenges in the California Encephalitis Project, 1998–2000. Clin Infect Dis 36(6):731–742
Hackett S, Hill L, Patel J et al (2009) Clinical characteristics of paediatric H1N1 admissions in Birmingham, UK. Lancet 374(9690):605
Haktanir A (2010) MR imaging in novel influenza A(H1N1)-associated meningoencephalitis. AJNR Am J Neuroradiol 31(3):394–395
HPA (2009) Swine-Lineage influenza A H1 specific fast real time PCR. National standard methods. Virology VSOP 29(2): Available at: http://www.hpa-standardmethods.org.uk/pdfsops.asp. Accessed on: July 2010)
Iwata A, Matsubara K, Nigami H et al (2010) Reversible splenial lesion associated with novel influenza A (H1N1) viral infection. Pediatr Neurol 42:447–450
Jelliffe S (1918) Nervous and mental disturbances of Influenza. N Y Med J 108:725–8, 55–57, 807–11
Kasai T, Togashi T, Morishima T (2000) Encephalopathy associated with influenza epidemics. Lancet 355(9214):1558–1559
Kawai N, Ikematsu H, Iwaki N et al (2008) A comparison of the effectiveness of zanamivir and oseltamivir for the treatment of influenza A and B. J Infect 56(1):51–57
Kullnat MW, Morse RP (2008) Choreoathetosis after herpes simplex encephalitis with basal ganglia involvement on MRI. Pediatrics 121(4):e1003–e1007
Leigh AD (1946) Infections of the nervous system occurring during an epidemic of influenza B. Br Med J 2(4485):936–938
Lister P, Reynolds F, Parslow R et al (2009) Swine-origin influenza virus H1N1, seasonal influenza virus, and critical illness in children. Lancet 374(9690):605–607
Lyon JB, Remigio C, Milligan T et al (2010) Acute necrotizing encephalopathy in a child with H1N1 influenza infection. Pediatr Radiol 40(2):200–205
Mariotti P, Iorio R, Frisullo G et al (2010) Acute necrotizing encephalopathy during novel influenza A (H1N1) virua infection. Ann Neurol 68:111–114
Maricich SM, Neul JL, Lotze TE et al (2004) Neurologic complications associated with influenza A in children during the 2003–2004 influenza season in Houston, Texas. Pediatrics 114(5):e626–e633
Martin A, Reade EP (2010) Acute necrotizing encephalopathy progressing to brain death in a pediatric patient with novel influenza A (H1N1) infection. Clin Infect Dis 50(8):e50–e52
Matheson NJ, Harnden AR, Perera R et al (2007) Neuraminidase inhibitors for preventing and treating influenza in children. Cochrane Database Syst Rev (1):CD002744
Morishima T, Togashi T, Yokota S et al (2002) Encephalitis and encephalopathy associated with an influenza epidemic in Japan. Clin Infect Dis 35(5):512–517
Newland JG, Romero JR, Varman M et al (2003) Encephalitis associated with influenza B virus infection in 2 children and a review of the literature. Clin Infect Dis 36(7):e87–e95
Okumura A, Abe S, Kidokoro H et al (2009) Acute necrotizing encephalopathy: a comparison between influenza and non-influenza cases. Microbiol Immunol 53(5):277–280
O’Leary MF, Chappell JD, Stratton CW et al (2010) Complex febrile seizures followed by complete recovery in an infant with high-titre 2009 pandemic influenza A (H1N1) virus infection. J Clin Microbiol 48(10):3803–3805
O’Riordan S, Barton M, Yau Y et al (2010) Risk factors and outcomes among children admitted to hospital with pandemic H1N1 influenza. CMAJ 182(1):39–44
Ormitti F, Ventura E, Summa A et al (2010) Acute necrotizing encephalopathy in a child during the 2009 influenza A (H1N1) pandemia: MR imaging in diagnosis and follow-up. AJNR Am J Neuroradiol 31(3):396–400
Oxford JS (2000) Influenza A pandemics of the 20th century with special reference to 1918: virology, pathology and epidemiology. Rev Med Virol 10(2):119–133
Pandemic (H1N1) 2009 - update 112, World Heatlh Organisation. http://www.who.int/csr/don/2010_08_06/en/index.html (accessed Aug 2010)
Rellosa N, Bloch KC, Shane AL et al (2010) Neurologic manifestations of pediatric novel H1N1 influenza infection. Pediatr Infect Dis J. Aug 31. [Epub ahead of print] doi: 10.1097/INF.0b013e3181f2de6f
Ryan MM, Procopis PG, Ouvrier RA (1999) Influenza A encephalitis with movement disorder. Pediatr Neurol 21(3):669–673
Sachedina N, Donaldson LJ (2010) Paediatric mortality related to pandemic influenza A H1N1 infection in England:an observational population-base study. Lancet. Published online 27th October 2010. doi:10.1016/S0140-6736(10)61195-6
Sánchez-Torrent L, Triviño-Rodriguez M, Suero-Toledano P et al (2010) Novel influenza A (H1N1) encephalitis in a 3-month-old infant. Infection 38(3):227–229
Steininger C, Popow-Kraupp T, Laferl H et al (2003) Acute encephalopathy associated with influenza A virus infection. Clin Infect Dis 36(5):567–574
Tan K, Prerna A, Leo YS (2010) Surveillance of H1N1-related neurological complications. Lancet Neurol 9(2):142–143
Troedson C, Gill D, Dale RC (2008) Emergence of acute necrotising encephalopathy in Australia. J Paediatr Child Health 44(10):599–601
Webster RI, Hazelton B, Suleiman J et al (2010) Severe encephalopathy with swine origin influenza A H1N1 infection in childhood: case reports. Neurology 74(13):1077–1078
Wong AM, Simon EM, Zimmerman RA et al (2006) Acute necrotizing encephalopathy of childhood: correlation of MR findings and clinical outcome. AJNR Am J Neuroradiol 27(9):1919–1923
Yildizdas D, Kendirli T, Arslankoylu AE et al (2010) Neurological complications of pandemic influenza (H1N1) in children. Eur J Pediatr Nov 26 [Epub ahead of print] doi:10.1007/s00431-010-1352-y
Yoshikawa H, Yamazaki S, Watanabe T et al (2001) Study of influenza-associated encephalitis/encephalopathy in children during the 1997 to 2001 influenza seasons. J Child Neurol 16(12):885–890
We are thankful to Dr. Keith Pohl, Dr. Elaine Hughes, Dr. Jean-Pierre Lin, Dr. Nuria Martinez-Alier, Dr. Claire Lundy, Dr. Tammy Hedderly, Dr. John Jackman, Dr. Artemis Gika and Dr. Karine Lascelles who were all closely involved in the care and management of these patients and for their helpful comments on this manuscript. We would also like to thank Dr. Atta Siddiqui for reviewing all the neuroimaging; Dr. Sushma Goyal for reviewing the electroencephalograms; Dr. Eithne MacMahon and Dr. Emma Aarons for assistance with virology; and Dr. Ruth Ackers for help with the dosing of zanamivir.
Conflicts of interest
The authors declare that they have no conflict of interest.
The authors Pinki Surana and Shan Tang contributed equally to this article.
About this article
Cite this article
Surana, P., Tang, S., McDougall, M. et al. Neurological complications of pandemic influenza A H1N1 2009 infection: European case series and review. Eur J Pediatr 170, 1007–1015 (2011). https://doi.org/10.1007/s00431-010-1392-3
- Influenza A
- Neurologic outcome