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Treatment and outcome of children and adolescents with N-methyl-d-aspartate receptor encephalitis

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Abstract

The objective of this study is to describe the treatment and outcome of children and adolescents with N-methyl-d-aspartate receptor (NMDA-R) encephalitis. A retrospective study of children and adolescents with NMDA-R encephalitis was performed by the French Paraneoplastic Neurological Syndrome Reference Center between January 1, 2007 and December 31, 2012. The modified Rankin scale (mRS) was used to assess outcome. Thirty-six children and adolescents with NMDA-R encephalitis were studied. All of the patients received first-line immunotherapy (corticosteroids, intravenous immunoglobulins or plasma exchange), and 81 % received second-line immunotherapy (rituximab or cyclophosphamide). Median time between first-line and second-line treatment was 26 days. During the first 24 months, 30 of 36 patients (83 %) achieved a good outcome (mRS ≤ 2) and 20 of 36 patients (56 %) achieved complete recovery (mRS = 0). Median time to good outcome and to complete recovery was 6 and 24 months, respectively. Three patients (8 %) relapsed, one patient died. In multivariate analysis, age >12 years was a predictor of good outcome and initial mRS ≤ 3 was a predictor of complete recovery. Despite a higher rate of patients who received second-line immunotherapy, the outcome of the patients in the present series was very similar to the outcome reported in previous series. The present study highlights the need for clinical trials to determine the optimal treatment of NMDA-R encephalitis.

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References

  1. Dalmau J, Tu E, 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. doi:10.1002/ana.21050

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. 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. doi:10.1002/ana.21756

    Article  PubMed Central  PubMed  Google Scholar 

  3. Irani SR, Bera K, Waters P, Zuliani L, Maxwell S, Zandi MS, Friese Ma, Galea I, Kullmann DM, Beeson D, Lang B, Bien CG, Vincent A (2010) N-methyl-d-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain 133:1655–1667. doi:10.1093/brain/awq113

    Article  PubMed Central  PubMed  Google Scholar 

  4. Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R (2011) Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 10:63–74. doi:10.1016/S1474-4422(10)70253-2

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J (2013) Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 12:157–165. doi:10.1016/S1474-4422(12)70310-1

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Armangue T, Titulaer MJ, Málaga I, Bataller L, Gabilondo I, Graus F, Dalmau J (2013) Pediatric anti-N-methyl-d-aspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients. J Pediatr 162:850–856. doi:10.1016/j.jpeds.2012.10.011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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. doi:10.1136/archdischild-2014-306795

    Google Scholar 

  8. Mikasova L, De Rossi P, Bouchet D, Georges F, Rogemond V, Didelot A, Meissirel C, Honnorat J, Groc L (2012) Disrupted surface cross-talk between NMDA and Ephrin-B2 receptors in anti-NMDA encephalitis. Brain 135:1606–1621. doi:10.1093/brain/aws092

    Article  PubMed  Google Scholar 

  9. Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Dessain SK, Rosenfeld MR, Balice-gordon R, Lynch DR (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7:1091–1098. doi:10.1016/S1474-4422(08)70224-2.Anti-NMDA-receptor

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Hacohen Y, Absoud M, Hemingway C, Jacobson L, Lin J-P, Pike M, Pullaperuma S, Siddiqui A, Wassmer E, Waters P, Irani SR, Buckley C, Vincent A, Lim M (2014) NMDA receptor antibodies associated with distinct white matter syndromes. Neurol Neuroimmunol Neuroinflamm 1:e2. doi:10.1212/NXI.0000000000000002

    Article  PubMed Central  PubMed  Google Scholar 

  11. Dale RC, Brilot F, Duffy LV, Twilt M, Waldman AT, Narula S, Muscal E, Deiva K, Andersen E, Eyre MR, Eleftheriou D, Brogan Pa, Kneen R, Alper G, Anlar B, Wassmer E, Heineman K, Hemingway C, Riney CJ, Kornberg A, Tardieu M, Stocco A, Banwell B, Gorman MP, Benseler SM, Lim M (2014) Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology 83:142–150. doi:10.1212/WNL.0000000000000570

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Manto M, Dalmau J, Didelot A, Rogemond V, Honnorat J (2010) In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic dysfunction. Orphanet J Rare Dis 5:31. doi:10.1186/1750-1172-5-31

    Article  PubMed Central  PubMed  Google Scholar 

  13. Lancaster E, Dalmau J (2012) Neuronal autoantigens-pathogenesis, associated disorders and antibody testing. Nat Rev Neurol 8:380–390. doi:10.1038/nrneurol.2012.99

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Camdessanché J-P, Streichenberger N, Cavillon G, Rogemond V, Jousserand G, Honnorat J, Convers P, Antoine J-C (2011) Brain immunohistopathological study in a patient with anti-NMDAR encephalitis. Eur J Neurol 18:929–931. doi:10.1111/j.1468-1331.2010.03180.x

    Article  PubMed  Google Scholar 

  15. Martinez-Hernandez E, Horvath J, Shiloh-Malawsky Y, Sangha N, Martinez-Lage M, Dalmau J (2011) Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis. Neurology 77:589–593

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Kosmidis ML, Dalakas MC (2010) Practical considerations on the use of rituximab in autoimmune neurological disorders. Ther Adv Neurol Disord 3:93–105. doi:10.1177/1756285609356135

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Martin Mdel P, Cravens PD, Winger R, Kieseier BC, Cepok S, Eagar TN, Zamvil SS, Weber MS (2009) Depletion of B lymphocytes from cerebral perivascular spaces by rituximab. Arch Neurol 66:1016–1021

    PubMed  Google Scholar 

  18. Binstadt B, Caldas A, Turvey S, Weinstein H, Jackson J, Fuhlbrigge R, Sundel R (2003) Rituximab therapy for multisystem autoimmune diseases in pediatric patients. J Pediatr 143:598–604

    Article  CAS  PubMed  Google Scholar 

  19. Nowak RJ, Dicapua DB, Zebardast N, Goldstein JM (2011) Response of patients with refractory myasthenia gravis to rituximab: a retrospective study. Ther Adv Neurol Disord 4:259–266. doi:10.1177/1756285611411503

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Kim S-H, Huh S-Y, Lee SJ, Joung A, Kim HJ (2013) A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol 70:1110–1117. doi:10.1001/jamaneurol.2013.3071

    Article  PubMed  Google Scholar 

  21. Fekete R, Jankovic J (2012) Childhood stiff-person syndrome improved with rituximab. Case Rep Neurol 4:92–96. doi:10.1159/000339446

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Battaglia T, De Grandis E, Mirabelli-Badenier M, Boeri L, Morcaldi G, Barabino P, Intra C, Naselli F, Pistoia V, Veneselli E, Conte M (2012) Response to rituximab in 3 children with opsoclonus-myoclonus syndrome resistant to conventional treatments. Eur J Paediatr Neurol 16:192–195. doi:10.1016/j.ejpn.2011.05.013

    Article  PubMed  Google Scholar 

  23. Tatencloux S, Chretien P, Rogemond V, Honnorat J, Tardieu M, Deiva K (2015) Intrathecal treatment of anti-N-methyl-d-aspartate receptor encephalitis in children. Dev Med Child Neurol. 57(1):95–99.  doi:10.1111/dmcn.12545

    Article  PubMed  Google Scholar 

  24. DeSena AD, Greenberg BM, Graves D (2014) Three phenotypes of anti-N-methyl-d-aspartate receptor antibody encephalitis in children: prevalence of symptoms and prognosis. Pediatr Neurol 51:542–549. doi:10.1016/j.pediatrneurol.2014.04.030

    Article  PubMed  Google Scholar 

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Acknowledgments

We would like to thank all of the physicians, patients and relatives who helped to collect the clinical data. CSF samples were collected with the help of Neurobiotec Bank and the Hospices Civils de Lyon.

Conflicts of interest

On behalf of all authors, the corresponding authors state that there is no conflict of interest.

Ethical standard

This study has been approved by the institutional review board and ethics committee of the University Claude Bernard Lyon 1/Hospices Civils de Lyon.

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Author notes

    Authors and Affiliations

    1. French Reference Center of Paraneoplastic Neurological Syndromes, Hospices Civils de Lyon, Hôpital Neurologique, 69677, Bron, France

      Anastasia Zekeridou, Evgenia Karantoni, Aurélien Viaccoz, François Ducray, Veronique Rogemond, Elodie Mathias, Géraldine Picard, Jean-Christophe Antoine & Jerome Honnorat

    2. Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR 5292, 69372, Lyon, France

      Aurélien Viaccoz, François Ducray, Veronique Rogemond, Elodie Mathias & Jerome Honnorat

    3. Université de Lyon, Université Claude Bernard Lyon 1, 69372, Lyon, France

      Aurélien Viaccoz, François Ducray & Jerome Honnorat

    4. Service de Neurologie Mazarin, Groupe Hospitalier Pitié-Salpêtrière, APHP, UMR S975, CNRS, UMR 7225, Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière, Université Pierre et Marie Curie-Paris 6, Paris, France

      Evgenia Karantoni & Jean-Yves Delattre

    5. Service de Neurologie Pédiatrique, Hôpital Necker Enfants Malades, APHP, INSERM U1016-CNRS8104, Université Paris-Descartes, Paris, France

      Cyril Gitiaux

    6. Service de Neurologie Pédiatrique, CHU Bordeaux, Bordeaux, France

      Frédéric Villega

    7. Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Sud, Neurologie Pédiatrique, Université Paris Sud et INSERM U1012, Orsay, France

      Kumaran Deiva & Marc Tardieu

    8. Service de Neurologie, CHU de Saint-Etienne et Université de Lyon, 42023, Saint-Etienne, France

      Jean-Christophe Antoine

    9. Neuro-Oncologie, Hôpital Neurologique Pierre Wertheimer, 59 Boulevard Pinel, 69677, Bron Cedex, France

      Jerome Honnorat

    Authors
    1. Anastasia Zekeridou
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    2. Evgenia Karantoni
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    3. Aurélien Viaccoz
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    4. François Ducray
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    7. Kumaran Deiva
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    8. Veronique Rogemond
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    9. Elodie Mathias
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    10. Géraldine Picard
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    11. Marc Tardieu
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    12. Jean-Christophe Antoine
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    13. Jean-Yves Delattre
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    14. Jerome Honnorat
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    Corresponding authors

    Correspondence to Anastasia Zekeridou or Jerome Honnorat.

    Additional information

    Anastasia Zekeridou and Evgenia Karantoni contributed equally to the manuscript.

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    Zekeridou, A., Karantoni, E., Viaccoz, A. et al. Treatment and outcome of children and adolescents with N-methyl-d-aspartate receptor encephalitis. J Neurol 262, 1859–1866 (2015). https://doi.org/10.1007/s00415-015-7781-9

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    • DOI: https://doi.org/10.1007/s00415-015-7781-9

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