Anti-NMDAR Antibodies in Demyelinating Diseases

Authors: M. Elišák 1;  E. Meluzínová 1;  J. Hanzalová 1,2;  P. Lišková 1;  D. Krýsl 3;  I. Doležalová 4;  I. Štětkářová 5;  P. Marusič 1
Authors‘ workplace: Neurologická klinika 2. LF UK a FN Motol, Praha 1;  Ústav imunologie, 2. LF UK a FN Motol, Praha 2;  Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 3;  1. neurologická klinika LF MU a FN u sv. Anny v Brně 4;  Neurologická klinika 3. LF UK a FN Královské Vinohrady, Praha 5
Published in: Cesk Slov Neurol N 2017; 80/113(3): 332-335
Category: Short Communication


Antibodies against N-methyl D-aspartate receptor (anti-NMDAR) are directly pathogenic autoantibodies associated with encephalitis. Cases reporting the presence of anti-NMDAR antibodies associated with a demyelinating disease have been published, some without symptoms of NMDAR encephalitis. The aim of our study was to describe characteristics of a demyelinating disease in patients with anti-NMDAR antibodies.

Material and methods:
Anti-NMDAR antibodies were investigated in the serum and cerebrospinal fluid of patients with clinically suspected autoimmune encephalitis by indirect immunofluorescence using cell-based assay on fixed cells transfected for the antigen. The clinical course and MRI findings consistent with a demyelinating disease were assessed in accordance with the current diagnostic criteria.

Eleven patients with autoimmune encephalitis and positive anti-NMDAR were identified between 2012 to 2015. Ten of them met criteria of NMDAR encephalitis, one patient had an acute onset (de novo status epilepticus) with MRI and CSF findings corresponding with acute disseminated encephalomyelitis and regression following corticosteroid treatment. Subsequently, due to MRI dynamics, this patient met the criteria of multiple sclerosis. One patient with NMDAR encephalitis developed an optic neuritis 20 months later and MRI showed demyelinating changes with dissemination in time and space. Following corticosteroid and azathioprine treatment, the patient is clinically stable but with persisting MRI disease activity. In both patients, demyelinating lesions were also identified in the spinal cord.

In patients with an atypical manifestation of a demyelinating disease (prominent psychiatric or cognitive symptoms, seizures or extrapyramidal signs) anti-NMDAR testing should be performed and an appropriate immunotherapy should be started in positive cases. In some patients, NMDAR encephalitis may result in an onset of a demyelinating disease.

Key words:
demyelinating disease – anti-NMDAR

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Chinese summary - 摘要











脱髓鞘疾病 - 抗NMDAR


1. Ekizoglu E, Tuzun E, Woodhall M, et al. Investigation of neuronal autoantibodies in two dif­ferent focal epilepsy syndromes. Epilepsia 2014;55(3):414– 22. doi: 10.1111/ epi.12528.

2. Kayser MS, Titulaer MJ, Gresa-Ar­ribas N, et al. Frequency and characteristics of isolated psychiatric episodes in anti– N-methyl-d-aspartate receptor encephalitis. JAMA Neurol 2013;70(9):1133– 9.

3. Levite M. Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/ B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebel­lar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren‘s syndrome, schizophrenia, mania or stroke. These autoim­mune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor‘s expres­sion, impair glutamate-induced signal­ing and function, activate blood brain bar­rier endothelial cel­ls, kill neurons, damage the brain, induce behavioral/ psychiatric/ cognitive abnormalities and ataxia in animal models, and can be removed or silenced in some patients by im­munotherapy. J Neural Transm (Vien­na) 2014;121(8):1029– 75. doi: 10.1007/ s00702-014-1193-3.

4. Titulaer MJ, Höftberger R, Iizuka T, et al. Overlapp­ing demyelinat­ing syndromes and anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol 2014;75(3):411– 28.

5. Lekoubou A, Viaccoz A, Didelot A, et al. Anti-N-metyl-D-aspartate receptor encephalitis with acute dis­seminated encephalomyelitis-like MRI features. Eur J Neurol 2012;19(2):e16– 7. doi: 10.1111/ j.1468-1331.2011.03617.x.

6. Graus F, Titulaer MJ, Balu R, et al. A clinical approach to dia­gnosis of autoim­mune encephalitis. Lancet Neurol 2016;15(4):391– 404. doi: 10.1016/ S1474-4422(15)00401-9.

7. Polman CH, Reingold SC, Banwell B, et al. Dia­g­nostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011;69(2):292– 302. doi: 10.1002/ ana.22366.

8. Wingerchuk DM, Banwell B, Ben­nett JL, et al; International Panel for NMO Dia­gnosis. International consensus dia­gnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85(2):177– 89. doi: 10.1212/ WNL.0000000000001729.

9. Irani SR, Bera K, Waters P, et al. N-methyl-D-aspartate antibody encephalitis: temporal progres­sion of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain 2010;133(6):1655– 67. doi: 10.1093/ brain/ awq113.

10. Kruer MC, Koch TK, Bourdette DN, et al. NMDA receptor encephalitis mimick­ing seronegative neuromyelitis optica. Neurology 2010;74(18):1473– 5. doi: 10.1212/ WNL.0b013e3181dc1a7f.

11. Pen­nington C, Livingstone S, Santosh C, et al. N-methyl D-aspartate receptor antibody encephalitis as­sociated with myelitis. J Neurol Sci 2012;317(1– 2):151– 3. doi: 10.1016/ j.jns.2012.02.034.

12. Fleischmann R, Prüss H, Rosche B, et al. Severe cognitive impairment as­sociated with intrathecal antibodies to the NR1 subunit of the N-methyl-D-aspartate receptor in a patient with multiple sclerosis. JAMA Neurol 2015;72(1):96– 9. doi: 10.1001/ jamaneurol.2014.1817.

13. Ramberger M, Bsteh G, Schanda K, et al. NMDA receptor antibodies: a rare as­sociation in inflam­matory demyelinat­ing diseases. Neurol Neuroim­munol Neuroinflamm 2015;2(5):e141. doi: 10.1212/ NXI.0000000000000141.

14. Spadaro M, Gerdes LA, Krumbholz M, et al. Auto­antibodies to MOG in a distinct subgroup of adult multiple sclerosis. Neurol Neuroim­munol Neuroinflamm 2016;3(5):e257. doi: 10.1212/ NXI.0000000000000257.

15. Kim SH, Kim W, Li XF, et al. Does interferon beta treatment exacerbate neuromyelitis optica spectrum disorder? Mult Scler 2012;18(10):1480– 3.

16. Sørensen PS, Fazekas F, Lee M. Intravenous im­munoglobulin G or the treatment of relapsing-remitt­ing multiple sclerosis: a meta-analysis. Eur J Neurol 2002;9(6):557– 63.

17. Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013;12(2):157– 65. doi: 10.1016/ S1474-4422(12)70310-1.

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