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Journal of Pediatric Neurology 2017; 15(02): 084-089
DOI: 10.1055/s-0037-1599832
Case Report
Georg Thieme Verlag KG Stuttgart · New York

Clinical Course of N-Methyl-D-Aspartate Receptor Encephalitis and the Effectiveness of Cyclophosphamide Treatment

Piero Pavone
1   Unit of Pediatrics and Pediatric Emergency, University-Hospital “Policlinico-Vittorio Emanuele,” University of Catania, Catania, Italy
,
Raffaele Falsaperla
1   Unit of Pediatrics and Pediatric Emergency, University-Hospital “Policlinico-Vittorio Emanuele,” University of Catania, Catania, Italy
,
Martino Ruggieri
2   Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Alberto Verrotti
3   Department of Pediatrics, University of Perugia, Perugia, Italy
,
Riccardo Lubrano
1   Unit of Pediatrics and Pediatric Emergency, University-Hospital “Policlinico-Vittorio Emanuele,” University of Catania, Catania, Italy
,
Renata Rizzo
2   Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Salomone Salomone
4   Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
,
Andrea D. Praticò
2   Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
4   Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
› Author Affiliations
Further Information

Publication History

19 November 2016

29 January 2017

Publication Date:
20 March 2017 (online)

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Abstract

We describe the cases of two unrelated girls, aged 5 and 7, respectively, affected by N-methyl-D-aspartate receptor (NMDAr) encephalitis. The clinical records of both patients were reviewed retrospectively including family and personal history, clinical findings, laboratory, and neuroradiological examinations, electroencephalogram, and treatment performed during admissions to the unit. In both patients, the clinical course was slow and progressive. Both showed anti-NMDAr antibodies in serum and cerebrospinal fluid. Treatment with intravenous immunoglobulin and methylprednisolone was not efficacious in the long term, with several relapses occurring in both patients. Second-line treatment with cyclophosphamide (1 g/m2 once a month) resulted in improvement of symptoms and disappearance of clinical signs that were sustained at 24 months follow-up. Side effects included neutropenia in one patient.

Keywords

NMDAr - encephalitis - intravenous immunoglobulins - steroids - cyclophosphamide
 

  • References

  • 1 Leypoldt F, Armangue T, Dalmau J. Autoimmune encephalopathies. Ann N Y Acad Sci 2015; 1338: 94-114
    CrossrefPubMedGoogle Scholar
  • 2 Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011; 10 (01) 63-74
    Google Scholar
  • 3 Florance NR, Davis RL, Lam C , et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009; 66 (01) 11-18
    CrossrefPubMedGoogle Scholar
  • 4 Dalmau J, Tüzün E, Wu HY , et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007; 61 (01) 25-36
    Google Scholar
  • 5 Granerod J, Ambrose HE, Davies NW , et al; UK Health Protection Agency (HPA) Aetiology of Encephalitis Study Group Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 2010; 10 (12) 835-844
    CrossrefPubMedGoogle Scholar
  • 6 Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA. The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis 2012; 54 (07) 899-904
    CrossrefPubMedGoogle Scholar
  • 7 Granerod J, Cousens S, Davies NW, Crowcroft NS, Thomas SL. New estimates of incidence of encephalitis in England. Emerg Infect Dis 2013; 19 (09) 1455-1462
    PubMedGoogle Scholar
  • 8 Dale RC, Irani SR, Brilot F , et al. N-methyl-D-aspartate receptor antibodies in pediatric dyskinetic encephalitis lethargica. Ann Neurol 2009; 66 (05) 704-709
    CrossrefPubMedGoogle Scholar
  • 9 Chanson JB, Diaconu M, Honnorat J , et al. PET follow-up in a case of anti-NMDAR encephalitis: arguments for cingulate limbic encephalitis. Epileptic Disord 2012; 14 (01) 90-93
    PubMedGoogle Scholar
  • 10 Bseikri MR, Barton JR, Kulhanjian JA , et al. Anti-N-methyl D-aspartate receptor encephalitis mimics viral encephalitis. Pediatr Infect Dis J 2012; 31 (02) 202-204
    CrossrefPubMedGoogle Scholar
  • 11 Armangue T, Titulaer MJ, Málaga I , et al; on behalf of the Spanish anti-NMDAR Encephalitis Work Group. Pediatric anti-N-methyl-Daspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients. J Pediatr 2013; 162: 850-856
    CrossrefPubMedGoogle Scholar
  • 12 Finke C, Kopp UA, Scheel M , et al. Functional and structural brain changes in anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol 2013; 74 (02) 284-296
    PubMedGoogle Scholar
  • 13 Wright S, Hacohen Y, Jacobson L , et al. N-methyl-D-aspartate receptor antibody-mediated neurological disease: results of a UK-based surveillance study in children. Arch Dis Child 2015; 100 (06) 521-526
    CrossrefPubMedGoogle Scholar
  • 14 Dale RC, Brilot F, Duffy LV , et al. Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology 2014; 83 (02) 142-150
    CrossrefPubMedGoogle Scholar
  • 15 Harward LE, Mitchell K, Pieper C, Copland S, Criscione-Schreiber LG, Clowse ME. The impact of cyclophosphamide on menstruation and pregnancy in women with rheumatologic disease. Lupus 2013; 22 (01) 81-86
    CrossrefPubMedGoogle Scholar