Skip to main content

Advertisement

Log in

Anti-NMDAR Encephalitis with Relapsing Optic Neuritis

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

Autoimmune encephalitis with antibodies to NMDA receptors (anti-NMDAR encephalitis) is a frequent form of autoimmune encephalitis. The disease is curable, though the lack of timely treatment can lead to disability in patients or death. Difficulties in the diagnosis of anti-NMDAR encephalitis arise from its heterogenous manifestations, its possible combination with other autoimmune diseases, and lack of doctors’ awareness of this type of encephalitis. This article reviews published data and describes a case of anti-NMDAR encephalitis with atypical features in the form of relapsing optic neuritis; it was difficult to link optic nerve lesions with comorbidity with multiple sclerosis or optic neuromyelitis spectrum disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. R. Vitaliani, W. Mason, B. Ances, et al., “Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma,” Ann. Neurol., 58, No. 4, 594–604 (2005), https://doi.org/10.1002/ana.20614.

    Article  PubMed  PubMed Central  Google Scholar 

  2. J. Dalmau, E. Tüzün, H. Wu, J. Masjuan, et al., “Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma,” Ann. Neurol., 61, No. 1, 25–36 (2007), https://doi.org/10.1002/ana.21050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. F. Graus, M. J. Titulaer, R. Balu, and J. Dalmau, “A clinical approach to diagnosis of autoimmune encephalitis,” Lancet Neurol., 15, No. 4, 391–404 (2016), https://doi.org/10.1016/S1474-4422(15)00401-9.

    Article  PubMed  PubMed Central  Google Scholar 

  4. J. Dalmau, E. Lancaster, E. Martinez-Hernandez, et al., “Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis,” Lancet Neurol., 10, No. 1, 63–74 (2011), https://doi.org/10.1016/S1474-4422(10)70253-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. T. Iizuka, F. Sakai, T. Ide, et al., “Anti-NMDA receptor encephalitis in Japan: Long-term outcome without tumor removal,” Neurology, 70, No. 7, 504–511 (2008).

    Article  CAS  Google Scholar 

  6. E. Tuzune and J. Dalmau, “Limbic encephalitis and variants: classification, diagnosis and treatment,” Neurologist, 13, No. 5, 261–271 (2007).

    Article  Google Scholar 

  7. M. Gastaldi, M. Nosadini, M. Spatola, et al., “N-methyl-D-aspartate receptor encephalitis: laboratory diagnostics and comparative clinical features in adults and children,” Expert Rev. Mol. Diagn., 18, No. 2, 181–193 (2018), https://doi.org/10.1080/14737159.2018.143112.

    Article  CAS  PubMed  Google Scholar 

  8. M. Guasp and J. Dalmau, “Encephalitis associated with antibodies against the NMDA receptor,” Med. Clin. (Barc.), 151, No. 2, 71–79 (2018), https://doi.org/10.1016/j.medcli.2017.10.015.

    Article  Google Scholar 

  9. M. J. Titulaer, R. Höftberger, T. Iizuka, et al., “Overlapping demyelinating syndromes and anti-N-methyl-d-aspartate receptor encephalitis,” Ann. Neurol., 75, No. 3, 411–428 (2014).

    Article  CAS  Google Scholar 

  10. M. Zoccarato, M. V. Saddi, G. Serra, et al., “Aquaporin-4 antibody neuromyelitis optica following anti-NMDA receptor encephalitis,” J. Neurol., 260, No. 12, 3185–3187 (2013), https://doi.org/10.1007/s00415-013-7182-x.

    Article  PubMed  Google Scholar 

  11. S. Fan, Y. Xu, H. Ren, et al., “Comparison of myelin oligodendrocyte glycoprotein (MOG)-antibody disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD) when they co-exist with anti-NMDA (N-methyl-D-aspartate) receptor encephalitis,” Mult. Scler. Relat. Disord., 20, 144–152 (2018), https://doi.org/10.1016/j.msard.2018.01.007.

    Article  PubMed  Google Scholar 

  12. E. E. Vasenina, O. S. Levin, O. A. Gan’kina, et al., “Autoimmune encephalitis with antibodies to NMDA receptors,” Zh. Nevrol. Psikhiatr., 117, No. 2, 111–116 (2017), https://doi.org/10.17116/jnevro201711721110-116.

    Article  Google Scholar 

  13. M. V. Davydovskaya, A. N. Boyko, I. A. Belyaeva, et al., “Autoimmune encephalitis,” Zh. Nevrol. Psikhiatr., M. V. 115, No. 4, 95–101 (2015), https://doi.org/10.17116/jnevro20151154195-101.

    Article  CAS  Google Scholar 

  14. C. Y. Liu, J. Zhu, X. Y. Zheng, et al., “Anti-N-methyl-D-aspartate receptor encephalitis: A severe, potentially reversible autoimmune encephalitis,” Mediators Inflamm., 6361479 (2017), https://doi.org/10.1155/2017/6361479.

  15. F. Inayat, W. A. Hung Pinto, S. Ahmad, et al., “Anti-N-methyl-Daspartate receptor encephalitis associated with ictal torsades de pointes and cardiac arrest,” Cureus, 11, No. 6, e4837 (2019), https://doi.org/10.7759/cureus.4837.

    Article  PubMed  PubMed Central  Google Scholar 

  16. D. R. Lynch, N. J. Anegawa, T. Verdoorn, and D. B. Pritchett, “N-methyl-D-aspartate receptors: different subunit requirements for binding of glutamate antagonists, glycine antagonists, and channel-blocking agents,” Mol. Pharmacol., 45, No. 3, 540–545 (1994).

    CAS  PubMed  Google Scholar 

  17. P. Paoletti, C. Bellone, and O. Zhou, “NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease,” Nat. Rev. Neurosci., 14, No. 6, 383–400 (2013).

    Article  CAS  Google Scholar 

  18. S. A. Lipton, “NMDA receptors, glial cells, and clinical medicine,” Neuron, 50, 9–11 (2006).

    Article  CAS  Google Scholar 

  19. E. Tüzün, L. Zhou, J. M. Baehring, et al., “Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma,” Acta Neuropathol., 118, 737–743 (2009).

    Article  Google Scholar 

  20. E. Martinez-Hernandez, J. Horvath, Y. Shiloh-Malawsky, et al., “Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis,” Neurology, 77, No. 6, 589–593 (2011), https://doi.org/10.1212/WNL.0b013e318228c136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. C. Li, L. Xiao, X. Liu, et al., “A functional role of NMDA receptor in regulating the differentiation of oligodendrocyte precursor cells and remyelination,” Glia, 61, No. 5, 732–749 (2013), https://doi.org/10.1002/glia.22469.

    Article  PubMed  Google Scholar 

  22. K. Miya, Y. Takahashi, and H. Mori, “Anti-NMDAR autoimmune encephalitis,” Brain Dev., 36, 645–652 (2014), https://doi.org/10.1016/j.braindev.2013.10.005.

    Article  PubMed  Google Scholar 

  23. J. Dalmau, A. J. Gleichman, E. G. Hughes, et al., “Anti-NMDAreceptor encephalitis: case series and analysis of the effects of antibodies,” Lancet Neurol., 7, No. 12, 1091–1098 (2008), https://doi.org/10.1016/S1474-4422(08)70224-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. E. H. Moscato, X. Peng, A. Jain, et al., “Acute mechanisms underlying antibody effects in anti-N-methyl-D-aspartate receptor encephalitis,” Ann. Neurol., 76, No. 1, 108–119 (2014), https://doi.org/10.1002/ana.24195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. E. G. Hughes, X. Peng, A. J. Gleichman, et al., “Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis,” J. Neurosci., 30, No. 17, 5866–5875 (2010), https://doi.org/10.1523/JNEUROSCI.0167-10.2010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. M. Zandi, S. Irani, G. Follows, et al., “Limbic encephalitis associated with antibodies to the NMDA receptor in Hodgkin lymphoma,” Neurology, 73, No. 23, 2039–2040 (2009), https://doi.org/10.1212/wnl.0b013e3181c55e9b.

    Article  CAS  PubMed  Google Scholar 

  27. A. Lebas, B. Husson, A. Didelot, et al., “Expanding spectrum of encephalitis with NMDA receptor antibodies in young children,” J. Child Neurol., 25, No. 6, 742–745 (2009), https://doi.org/10.1177/0883073809343319.

    Article  PubMed  Google Scholar 

  28. M. J. Titulaer, L. McCracken, I. Gabilondo, et al., “Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study,” Lancet Neurol., 12, No. 2, 157–165 (2013), https://doi.org/10.1016/S1474-4422(12)70310-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. S. R. Irani, K. Bera, P. Waters, 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, 133, 1655–1667 (2010), https://doi.org/10.1093/brain/awq113.

    Article  PubMed  PubMed Central  Google Scholar 

  30. A. Desena, D. Graves, W. Warnack, and B. M. Greenberg, “Herpes simplex encephalitis as a potential cause of anti-N-methyl-D-aspartate receptor antibody encephalitis: report of 2 cases,” JAMA Neurol., 71, No. 3, 344–346 (2014).

    Article  Google Scholar 

  31. C. Ma, C. Wang, Q. Zhang, and Y. Lian, “Emerging role of prodromal headache in patients with anti-N-methyl-D-aspartate receptor encephalitis,” J. Pain Res., 30, No. 12, 519–526 (2019), https://doi.org/10.2147/JPR.S189301.

    Article  Google Scholar 

  32. H. E. Peery, G. S. Day, et al., “Anti-NMDA receptor encephalitis. The disorder, the diagnosis and the immunobiology,” Autoimmun. Rev., 11, 863–872 (2012), https://doi.org/10.1016/j.autrev.2012.03.001.

    Article  CAS  PubMed  Google Scholar 

  33. K. Qin, W. Wu, Y. Huang, et al., “Anti-N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis presents in atypical types and coexists with neuromyelitis optica spectrum disorder or neurosyphilis,” BMC Neurol., 17, 1 (2017), publ. online Jan 5, 2017, https://doi.org/10.1186/s12883-016-0787-9.

  34. N. R. Florance, R. L. Davis, C. Lam, et al., “Anti-N-methyl-Daspartate receptor(NMDAR) encephalitis in children and adolescents,” Ann. Neurol., 66, 11–18 (2009), https://doi.org/10.1002/ana.21756.

    Article  PubMed  PubMed Central  Google Scholar 

  35. I. Gabilondo, A. Saiz, L. Galán, et al., “Analysis of relapses in anti-NMDAR encephalitis,” Neurology, 77, No. 10, 996–999 (2011), https://doi.org/10.1212/WNL.0b013e31822cfc6b.

    Article  CAS  PubMed  Google Scholar 

  36. N. Gresa-Arribas, M. J. Titulaer, A. Torrents, et al., “Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study,” Lancet Neurol., 13, 167–177 (2014), https://doi.org/10.1016/S1474-4422(13)70282-5.

    Article  CAS  PubMed  Google Scholar 

  37. A. Viaccoz, V. Desestret, F. Ducray, et al., “Clinical specificities of adult male patients with NMDA receptor antibodies encephalitis,” Neurology, 82, 556–563 (2014), https://doi.org/10.1212/WNL.0000000000000126.

    Article  CAS  PubMed  Google Scholar 

  38. M. S. Zandi, R. W. Paterson, M. A. Ellul, et al., “Clinical relevance of serum antibodies to extracellular N-methyl-D-aspartate receptor epitopes,” J Neurol. Neurosurg. Psychiatry, 86, 708–713 (2015), https://doi.org/10.1136/jnnp-2014-308736.

    Article  PubMed  Google Scholar 

  39. R. Wang, H. Z. Guan, H. T. Ren, et al., “CSF findings in patients with anti-N-methyl-D-aspartate receptor-encephalitis,” Seizure, 29, 137–142 (2015), https://doi.org/10.1016/j.seizure.2015.04.005.

    Article  CAS  PubMed  Google Scholar 

  40. A. Waschbisch, B. Kallmünzer, S. Schwab, et al., “Demyelinating disease and anti-N-methyl-D-aspartate receptor immunoglobulin G antibodies: a case report,” BMC Res. Notes, 7, 948 (2015), https://www.biomedcentral.com/1756-0500/7/948.

    Article  Google Scholar 

  41. L. Dahm, C. Ott, J. Steiner, et al., “Seroprevalence of autoantibodies against brain antigens in health and disease,” Ann. Neurol., 76, 82–94 (2014), https://doi.org/10.1002/ana.24189.

    Article  CAS  PubMed  Google Scholar 

  42. N. Ishikawa, G. Tajima, S. Hyodo, et al., “Detection of autoantibodies against NMDA-type glutamate Receptor in a patient with recurrent optic neuritis and transient cerebral lesions,” Neuropediatrics, 38, No. 5, 257–260 (2007), https://doi.org/10.1055/s-2007-1004521.

    Article  CAS  PubMed  Google Scholar 

  43. S. Tao, Y. Zhang, H. Ye, and D. Guo, “AQP4-IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD) coexisting with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis: A case report and literature review,” Mult. Scler. Relat. Disord., 20, No. 35, 185–192 (2019), https://doi.org/10.1016/j.msard.2019.07.008.

    Article  Google Scholar 

  44. Y. Ran, L. Wang, F. Zhang, et al., “Anti-NMDAR encephalitis followed by seropositive neuromyelitis optica spectrum disorder: A case report and literature review,” Clin. Neurol. Neurosurg., 155, 75–82 (2017), https://doi.org/10.1016/j.clineuro.2017.02.016.

    Article  PubMed  Google Scholar 

  45. A. Takeda, H. Shimada, A. Tamura, et al., “A case of anti-N-methyl-D-aspartate receptor encephalitis with multiple sclerosis-like demyelinated lesions,” Mult. Scler. Relat. Disord., 3, No. 3, 391–397 (2014), https://doi.org/10.1016/j.msard.2013.09.005.

    Article  PubMed  Google Scholar 

  46. J. J. Luo, H. Lv, W. Sun, et al., “Anti-N-methyl-d-aspartate receptor encephalitis in a patient with neuromyelitis optica spectrum disorders,” Mult. Scler. Relat. Disord., 8, 74–77 (2016), https://doi.org/10.1016/j.msard.2016.05.002.

    Article  PubMed  Google Scholar 

  47. Y. Hacohen, M. Absoud, C. Hemingway, et al., “NMDA receptor antibodies associated with distinct white matter syndromes,” Neurol. Neuroimmunol. Neuroinflamm., 1, No. 1, e2 (2014), https://doi.org/10.1212/NXI.0000000000000002.

  48. K. Kaneko, D. K. Sato, T. Misu, et al., “Anti-N-methyl-D-aspartate receptor encephalitis with multiphasic demyelination,” Ann. Neurol., 76, No. 3, 462–464 (2014), https://doi.org/10.1002/ana.24224.

    Article  CAS  PubMed  Google Scholar 

  49. D. M. Wingerchuk, B. Banwell, J. L. Bennett, et al., “ International consensus diagnostic criteria for neuromyelitis optica spectrum disorders,” Neurology, 85, No. 2, 177–189 (2015), https://doi.org/10.1212/WNL.0000000000001729.

    Article  PubMed  PubMed Central  Google Scholar 

  50. S. Jarius, B. Wildemann, and F. Paul, “Neuromyelitis optica: clinical features, immunopathogenesis and treatment,” Clin. Exp. Immunol., 176, No. 2, 149–164 (2014), https://doi.org/10.1111/cei.12271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. M. C. Kruer, T. K. Koch, and D. N. Bourdette, “NMDA receptor encephalitis mimicking seronegative neuromyelitis optica,” Neurology, 74, No. 18, 1473–1475 (2010), https://doi.org/10.1212/WNL.0b013e3181dc1a7f.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. M. Jurynczyk, R. Geraldes, F. Probert, et al., “Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis,” Brain, 140, No. 3, 617–627 (2017), https://doi.org/10.1093/brain/aww350.

    Article  PubMed  Google Scholar 

  53. H. Ishiura, S. Matsuda, M. Higashihara, et al., “Response of anti-NMDA receptor encephalitis without tumor to immunotherapy including rituximab,” Neurology, 71, No. 23, 1921–1923 (2008), https://doi.org/10.1212/01.wnl.0000336648.43562.59.

    Article  CAS  PubMed  Google Scholar 

  54. M. Kadoya, H. Onoue, A. Kadoya, et al., “Refractory status epilepticus caused by anti-NMDA receptor encephalitis that markedly improved following combination therapy with rituximab and cyclophosphamide,” Intern. Med., 54, No. 2, 209–213 (2015), https://doi.org/10.2169/internalmedicine.54.2047.

    Article  PubMed  Google Scholar 

  55. K. Wang, Z. Chen, D. Wu, et al., “Early second-line therapy is associated with improved episodic memory in anti-NMDA receptor encephalitis,” Ann. Clin. Transl. Neurol., 6, No. 7, 1202–1213 (2019), https://doi.org/10.1002/acn3.50798.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. M. Casares, H. J. Skinner, E. D. Gireesh, et al., “Successful intrathecal rituximab administration in refractory nonteratoma anti-N-methyl-D-aspartate receptor encephalitis: A case report,” J. Neurosci. Nurs., 51, No. 4, 194–197 (2019), https://doi.org/10.1097/JNN.0000000000000450.

    Article  PubMed  Google Scholar 

  57. S. Masghati, M. Nosratian, and O. Dorigo, “Anti-N-methyl-aspartate receptor encephalitis in identical twin sisters: role for oophorectomy,” Obstet. Gynecol., 123, No. 2, 433–435 (2014);

    Article  CAS  Google Scholar 

  58. M. P. Malter, C. Frisch, J. C. Schoene-Bake, et al., “Outcome of limbic encephalitis with VGKC-complex antibodies: relation to antigenic specificity,” J. Neurol., 261, No. 9, 1695–1705 (2014), https://doi.org/10.1007/s00415-014-7408-6.

    Article  CAS  PubMed  Google Scholar 

  59. J. A. Lim, S. T. Lee, K. H. Jung, et al., “Anti-N-methyl-D-aspartate receptor encephalitis in Korea: clinical features, treatment, and outcome,” J. Clin. Neurophysiol., 10, No. 2, 157–161 (2014), https://doi.org/10.3988/jcn.2014.10.2.157.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. N. Belova.

Additional information

Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 120, No. 6, Iss. 1, pp. 105–113, June, 2020.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Belova, A.N., Grygorieva, V.N., Rasteryaeva, M.V. et al. Anti-NMDAR Encephalitis with Relapsing Optic Neuritis. Neurosci Behav Physi 51, 163–170 (2021). https://doi.org/10.1007/s11055-021-01053-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-021-01053-x

Keywords

Navigation