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

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Abstract

Purpose

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.

Methods

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

Results

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.

Conclusions

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.

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References

  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 61:25–36

    Article  CAS  Google Scholar 

  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 13:167–177

    Article  Google Scholar 

  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 10:835–844

    Article  Google Scholar 

  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 22:135–142

    Article  Google Scholar 

  5. Borlot F, Santos MLF, Bandeira M et al (2012) Anti-N-methyl D-aspartate receptor encephalitis in childhood. J Pediatr 88:275–278

    Google Scholar 

  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):473–479

  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 100:521–526

    Article  Google Scholar 

  8. de Bruijn MAAM, Aarsen FK, van Oosterhout MP et al (2018) Long-term neuropsychological outcome following pediatric anti-NMDAR encephalitis. Neurology 90:e1997–e2005

    Article  Google Scholar 

  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 66:11–18

    Article  Google Scholar 

  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 66:704–709

    Article  CAS  Google Scholar 

  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 84:748–755

    Article  Google Scholar 

  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 19:453–463

    Article  Google Scholar 

  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 31:1150–1155

    Article  Google Scholar 

  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 312:59–65

    Article  CAS  Google Scholar 

  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 25:713–724

    Google Scholar 

  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 82:556–563

    Article  CAS  Google Scholar 

  17. Ignacio R-A, Josep D, Teresa S et al (2011) Isolated hemidystonia associated with NMDA receptor antibodies. Mov Disord 26:265–275

    Google Scholar 

  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 30:5866–5875

    Article  CAS  Google Scholar 

  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 39:19–23

    Article  Google Scholar 

  20. Guasp M, Dalmau J (2018) Encefalitis por anticuerpos contra el receptor de NMDA. Med Clin (Barc) 150:1–9

    Google Scholar 

  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 70:504–511

    Article  CAS  Google Scholar 

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Acknowledgements

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

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Authors and Affiliations

  1. Hospital Pequeno Príncipe, Curitiba, Paraná, Brazil

    Daniel Almeida do Valle, Joselainy Stela Pires Galeazzi, Alfredo Lohr Júnior & Mara Lúcia Schmitz Ferreira Santos

  2. Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Paraná, Brazil

    Daniel Almeida do Valle, Mayara de Rezende Machado, Alcir Francisco da Silva & Rosana Herminia Scola

  3. Hospital Geral Roberto Santos, Salvador, Brazil

    Vanessa Catarine Silva Abreu Ribeiro dos Santos

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  1. Daniel Almeida do Valle
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Correspondence to Daniel Almeida do Valle.

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do Valle, D.A., Galeazzi, J.S.P., Machado, M.d. et al. Clinical variability of children with anti-N-methyl-d-aspartate receptor encephalitis in southern Brazil: a cases series and review of the literature. Neurol Sci 40, 351–356 (2019). https://doi.org/10.1007/s10072-018-3648-z

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  • DOI: https://doi.org/10.1007/s10072-018-3648-z

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