Treatment and outcome of children and adolescents with N-methyl-d-aspartate receptor encephalitis
- 1.5k Downloads
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.
KeywordsPediatric autoimmune encephalitis NMDA receptor encephalitis
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.
This study has been approved by the institutional review board and ethics committee of the University Claude Bernard Lyon 1/Hospices Civils de Lyon.
- 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 PubMedCentralCrossRefPubMedGoogle 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 PubMedCentralCrossRefPubMedGoogle 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 PubMedCentralCrossRefPubMedGoogle 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 PubMedCentralCrossRefPubMedGoogle 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 PubMedCentralCrossRefPubMedGoogle 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 PubMedCentralCrossRefPubMedGoogle 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 PubMedCentralCrossRefPubMedGoogle 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 PubMedCentralCrossRefPubMedGoogle 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 CrossRefPubMedGoogle Scholar