Neurological Sciences

, Volume 40, Issue 2, pp 351–356 | Cite as

Clinical variability of children with anti-N-methyl-d-aspartate receptor encephalitis in southern Brazil: a cases series and review of the literature

  • Daniel Almeida do ValleEmail author
  • Joselainy Stela Pires Galeazzi
  • Mayara de Rezende Machado
  • Vanessa Catarine Silva Abreu Ribeiro dos Santos
  • Alcir Francisco da Silva
  • Alfredo Lohr Júnior
  • Mara Lúcia Schmitz Ferreira Santos
  • Rosana Herminia Scola
Original Article



Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disease of the central nervous system (CNS). The aim of this study was to describe the variability of clinical presentation in anti-NMDAR encephalitis, treatment and outcomes in a case series of children and adolescents.


Retrospectively analyse patients diagnosed with anti-NMDAR encephalitis, from 2010 to 2018.


The study population consisted of nine children with anti-NMDAR encephalitis from southern Brazil, six females and three males, aged 5 months to 16 years (mean 5 years). The time of follow-up varied between 1 and 7 years, with a mean of 3 years. The most frequent first manifestation consisted of seizures. All patients described had psychiatric symptoms and a wide spectrum of neurologic findings. Five patients had unilateral symptoms. Magnetic resonance imaging and electroencephalogram were normal in most patients. Cerebrospinal fluid pleocytosis occurred in five patients. All patients were administered immunoglobulin and/or steroids. Seven patients (78%) required cyclophosphamide and/or rituximab. Almost half of the patients fully recovered from all symptoms.


A wide variety of symptoms were observed in this study and, although unilateral symptoms are rarely reported in the literature, a high frequency was observed among Brazilian children. Alternatives to first-line therapy should be considered in patients with clinical suspicion, even if they have not had a good response with first-line therapy.


Anti-N-methyl-d-aspartate receptor Encephalitis Paediatrics Autoimmune 



We would like to express our sincere gratitude to Prof. Josep Dalmau from the University of Barcelona and Prof. Lindsey McCracken from the University of Pennsylvania, for the antibody testing in our patients.

Authorship contributions

Daniel Almeida do Valle: acquisition of data, analysis and interpretation of data, revisions of the manuscript

Joselainy Stela Pires Galeazzi: acquisition of data, analysis and interpretation of data, revisions of the manuscript

Mayara de Rezende Machado: acquisition of data, analysis and interpretation of data

Vanessa Catarine Silva Abreu Ribeiro dos Santos: acquisition of data, analysis and interpretation of data

Alcir Francisco da Silva: analysis and interpretation of the data, critical revision of the manuscript

Alfredo Lohr Júnior: analysis and interpretation of the data, critical revision of the manuscript

Mara Lúcia Schmitz Ferreira Santos: study design, analysis and interpretation of the data, critical revision of the manuscript

Rosana Herminia Scola: study design, drafting and critical revision of the manuscript for important intellectual content

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Dalmau J, Tüzün E, Wu HY, Masjuan J, Rossi JE, Voloschin A, Baehring JM, Shimazaki H, Koide R, King D, Mason W, Sansing LH, Dichter MA, Rosenfeld MR, Lynch DR (2007) Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 61:25–36CrossRefGoogle Scholar
  2. 2.
    Gresa-arribas N, Titulaer MJ, Torrents A et al (2015) Diagnosis and significance of antibody titers in anti-NMDA receptor encephalitis, a retrospective study. Lancet Neurol 13:167–177CrossRefGoogle Scholar
  3. 3.
    Granerod J, Ambrose HE, Davies NWS, Clewley JP, Walsh AL, Morgan D, Cunningham R, Zuckerman M, Mutton KJ, Solomon T, Ward KN, Lunn MP, Irani SR, Vincent A, Brown DW, Crowcroft NS, UK Health Protection Agency (HPA) Aetiology of Encephalitis Study Group (2010) Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 10:835–844CrossRefGoogle Scholar
  4. 4.
    Konuskan B, Yildirim M, Topaloglu H, Erol I, Oztoprak U, Tan H, Gocmen R, Anlar B (2018) Clinical presentation of anti-N-methyl-D-aspartate receptor and anti-voltage-gated potassium channel complex antibodies in children: a series of 24 cases. Eur J Paediatr Neurol 22:135–142CrossRefGoogle Scholar
  5. 5.
    Borlot F, Santos MLF, Bandeira M et al (2012) Anti-N-methyl D-aspartate receptor encephalitis in childhood. J Pediatr 88:275–278Google Scholar
  6. 6.
    Ho AC, Chan SH, Chan E et al (2018) Anti-N-methyl-D-aspartate receptor encephalitis in children: incidence and experience in Hong Kong. Brain Dev 40(6):473–479Google Scholar
  7. 7.
    Wright S, Hacohen Y, Jacobson L, Agrawal S, Gupta R, Philip S, Smith M, Lim M, Wassmer E, Vincent A (2015) N-methyl-D-aspartate receptor antibody-mediated neurological disease: results of a UK-based surveillance study in children. Arch Dis Child 100:521–526CrossRefGoogle Scholar
  8. 8.
    de Bruijn MAAM, Aarsen FK, van Oosterhout MP et al (2018) Long-term neuropsychological outcome following pediatric anti-NMDAR encephalitis. Neurology 90:e1997–e2005CrossRefGoogle Scholar
  9. 9.
    Florance NR, Davis RL, Lam C, Szperka C, Zhou L, Ahmad S, Campen CJ, Moss H, Peter N, Gleichman AJ, Glaser CA, Lynch DR, Rosenfeld MR, Dalmau J (2009) Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 66:11–18CrossRefGoogle Scholar
  10. 10.
    Dale RC, Irani SR, Brilot F, Pillai S, Webster R, Gill D, Lang B, Vincent A (2009) N-methyl-D-aspartate receptor antibodies in pediatric dyskinetic encephalitis lethargica. Ann Neurol 66:704–709CrossRefGoogle Scholar
  11. 11.
    Hacohen Y, Wright S, Waters P, Agrawal S, Carr L, Cross H, de Sousa C, DeVile C, Fallon P, Gupta R, Hedderly T, Hughes E, Kerr T, Lascelles K, Lin JP, Philip S, Pohl K, Prabahkar P, Smith M, Williams R, Clarke A, Hemingway C, Wassmer E, Vincent A, Lim MJ (2013) Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry 84:748–755CrossRefGoogle Scholar
  12. 12.
    Sartori S, Nosadini M, Cesaroni E, Falsaperla R, Capovilla G, Beccaria F, Mancardi MM, Santangelo G, Giunta L, Boniver C, Cantalupo G, Cappellari A, Costa P, Dalla Bernardina B, Dilena R, Natali Sora MG, Pelizza MF, Pruna D, Serino D, Vanadia F, Vigevano F, Zamponi N, Zanus C, Toldo I, Suppiej A (2015) Paediatric anti-N-methyl-d-aspartate receptor encephalitis: the first Italian multicenter case series. Eur J Paediatr Neurol 19:453–463CrossRefGoogle Scholar
  13. 13.
    Brenton JN, Kim J, Schwartz RH (2016) Approach to the Management of Pediatric-Onset Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis. J Child Neurol 31:1150–1155CrossRefGoogle Scholar
  14. 14.
    Wang Y, Zhang W, Yin J, Lu Q, Yin F, He F, Peng J (2017) Anti-N-methyl-D-aspartate receptor encephalitis in children of Central South China: clinical features, treatment, influencing factors, and outcomes. J Neuroimmunol 312:59–65CrossRefGoogle Scholar
  15. 15.
    Armangue T, Titulaer MJ, Málaga I et al (2013) Pediatric anti-NMDAR encephalitis-clinical analysis and novel findings in a series of 20 patients. J Pediatr 25:713–724Google Scholar
  16. 16.
    Viaccoz A, Desestret V, Ducray F, Picard G, Cavillon G, Rogemond V, Antoine JC, Delattre JY, Honnorat J (2014) Clinical specificities of adult male patients with NMDA receptor antibodies encephalitis. Neurology 82:556–563CrossRefGoogle Scholar
  17. 17.
    Ignacio R-A, Josep D, Teresa S et al (2011) Isolated hemidystonia associated with NMDA receptor antibodies. Mov Disord 26:265–275Google Scholar
  18. 18.
    Hughes EG, Peng X, Gleichman AJ, Lai M, Zhou L, Tsou R, Parsons TD, Lynch DR, Dalmau J, Balice-Gordon RJ (2010) Cellular and synaptic mechanisms of anti-NMDAR encephalitis. J Neurosci 30:5866–5875CrossRefGoogle Scholar
  19. 19.
    Barry H, Byrne S, Barrett E, Murphy KC, Cotter DR (2015) Anti-N-methyl-D-aspartate receptor encephalitis: review of clinical presentation, diagnosis and treatment. BJPsych Bull 39:19–23CrossRefGoogle Scholar
  20. 20.
    Guasp M, Dalmau J (2018) Encefalitis por anticuerpos contra el receptor de NMDA. Med Clin (Barc) 150:1–9Google Scholar
  21. 21.
    Iizuka T, Sakai F, Ide T, Monzen T, Yoshii S, Iigaya M, Suzuki K, Lynch DR, Suzuki N, Hata T, Dalmau J (2008) Anti-NMDA receptor encephalitis in Japan: long-term outcome without tumor removal. Neurology 70:504–511CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  • Daniel Almeida do Valle
    • 1
    • 2
    Email author
  • Joselainy Stela Pires Galeazzi
    • 1
  • Mayara de Rezende Machado
    • 2
  • Vanessa Catarine Silva Abreu Ribeiro dos Santos
    • 3
  • Alcir Francisco da Silva
    • 2
  • Alfredo Lohr Júnior
    • 1
  • Mara Lúcia Schmitz Ferreira Santos
    • 1
  • Rosana Herminia Scola
    • 2
  1. 1.Hospital Pequeno PríncipeCuritibaBrazil
  2. 2.Hospital de Clínicas da Universidade Federal do ParanáCuritibaBrazil
  3. 3.Hospital Geral Roberto SantosSalvadorBrazil

Personalised recommendations