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.
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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.
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.
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.
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.
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).
E. Tuzune and J. Dalmau, “Limbic encephalitis and variants: classification, diagnosis and treatment,” Neurologist, 13, No. 5, 261–271 (2007).
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.
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.
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).
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.
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.
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.
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.
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.
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.
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).
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).
S. A. Lipton, “NMDA receptors, glial cells, and clinical medicine,” Neuron, 50, 9–11 (2006).
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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);
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.
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.
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Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 120, No. 6, Iss. 1, pp. 105–113, June, 2020.
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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
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DOI: https://doi.org/10.1007/s11055-021-01053-x