Anti-NMDA Receptor Encephalitis: Efficacy of Treatment for Male Patients and miRNA Biomarker

Author(s): Hsiuying Wang*

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 24 , 2020

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Abstract:

Background: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an acute form of encephalitis. Treatments for the anti-NMDA receptor encephalitis usually include steroids, intravenous immunoglobulin, plasma exchange, plasmapheresis, rituximab, cyclophosphamide and tumor resection.

Objective: We aimed to compare the efficacy of the treatments including intravenous immunoglobulin, plasma exchange, plasmapheresis, rituximab or cyclophosphamide for male anti- NMDA receptor encephalitis patients without tumor and to discuss potential biomarkers for this disease.

Method: The Fisher exact test and the contingency table analysis were used to analyze the treatment efficacy for 43 male and 76 female patients. In addition, a hierarchical tree method was adopted to analyze the difference in the treatment efficacy between male and female patients.

Results: The p-values of testing whether the efficacy rate of plasmapheresis (or plasma exchange) for the male patient is greater than a threshold are significantly different from the pvalues for the other two treatments. In addition, the hierarchical tree method shows that the treatment strategy associating with early recovery is different for male and female patients.

Conclusion: The results revealed that the efficacy rate of plasmapheresis (or plasma exchange) is not inferior to that of intravenous immunoglobulin and rituximab (or cyclophosphamide) for male patients without tumor. In addition, B-cell attracting C-X-C motif chemokine 13 (CXCL13) and microRNA let-7b have the potential to be the treatment response biomarkers for anti-NMDA receptor encephalitis. They may not be useful prognostic biomarkers for this encephalitis unless they are not biomarkers for other autoimmune encephalitides.

Keywords: anti-NMDA receptor encephalitis, immunotherapy, efficacy rate, treatment, chemokine 13, microRNA.

[1]
Srebro, D.; Vučković, S.; Milovanović, A.; Košutić, J.; Vujović, K.S.; Prostran, M. Magnesium in pain research: state of the art. Curr. Med. Chem., 2017, 24(4), 424-434.
[PMID: 27978803]
[2]
Dalmau, J.; Tüzün, E.; Wu, H.Y.; Masjuan, J.; Rossi, J.E.; Voloschin, A.; Baehring, J.M.; Shimazaki, H.; Koide, R.; King, D.; Mason, W.; Sansing, L.H.; Dichter, M.A.; Rosenfeld, M.R.; Lynch, D.R. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann. Neurol., 2007, 61(1), 25-36.
[http://dx.doi.org/10.1002/ana.21050] [PMID: 17262855]
[3]
Dalmau, J.; Gleichman, A.J.; Hughes, E.G.; Rossi, J.E.; Peng, X.; Lai, M.; Dessain, S.K.; Rosenfeld, M.R.; Balice-Gordon, R.; Lynch, D.R. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol., 2008, 7(12), 1091-1098.
[http://dx.doi.org/10.1016/S1474-4422(08)70224-2] [PMID: 18851928]
[4]
Wang, H. Anti-NMDA receptor encephalitis and vaccination. Int. J. Mol. Sci., 2017, 18(1)E193
[http://dx.doi.org/10.3390/ijms18010193] [PMID: 28106787]
[5]
Titulaer, M.J.; McCracken, L.; Gabilondo, I.; Armangué, T.; Glaser, C.; Iizuka, T.; Honig, L.S.; Benseler, S.M.; Kawachi, I.; Martinez-Hernandez, E.; Aguilar, E.; Gresa-Arribas, N.; Ryan-Florance, N.; Torrents, A.; Saiz, A.; Rosenfeld, M.R.; Balice-Gordon, R.; Graus, F.; Dalmau, J. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol., 2013, 12(2), 157-165.
[http://dx.doi.org/10.1016/S1474-4422(12)70310-1] [PMID: 23290630]
[6]
Shah, N.N. Antibody based therapies in acute leukemia. Curr. Drug Targets, 2017, 18(3), 257-270.
[http://dx.doi.org/10.2174/1389450117666160905091459] [PMID: 27593687]
[7]
Witkowska, M.; Smolewski, P. Development of Anti-CD20 antigen-targeting therapies for B-cell lymphoproliferative malignancies - the state of the art. Curr. Drug Targets, 2016, 17(9), 1072-1082.
[http://dx.doi.org/10.2174/1389450116666150907105306] [PMID: 26343115]
[8]
Sebastiani, M.; Giuggioli, D.; Colaci, M.; Fallahi, P.; Gragnani, L.; Antonelli, A.; Zignego, A.L.; Ferri, C. HCV-related rheumatic manifestations and therapeutic strategies. Curr. Drug Targets, 2017, 18(7), 803-810.
[http://dx.doi.org/10.2174/1389450116666150907103622] [PMID: 26343108]
[9]
Giuggioli, D.; Sebastiani, M.; Colaci, M.; Fallahi, P.; Gragnani, L.; Zignego, A.L.; Antonelli, A.; Ferri, C. Treatment of HCV-related mixed cryoglobulinemia. Curr. Drug Targets, 2017, 18(7), 794-802.
[http://dx.doi.org/10.2174/1389450116666150825112105] [PMID: 26302805]
[10]
Risitano, A.M. Withdrawn: aplastic anemia: alternative immunosuppressive treatments and eltrombopag. A report from the 2014 EBMT educational meeting from the severe aplastic anaemia and infectious diseases working parties. Curr. Drug Targets, 2015..
[PMID: 25619749]
[11]
Wang, H. Efficacies of treatments for anti-NMDA receptor encephalitis. Front. Biosci., 2016, 21, 651-663.
[http://dx.doi.org/10.2741/4412] [PMID: 26709797]
[12]
Rosenfeld, M.R. Antibody-mediated central nervous system diseases: disease recognition and treatment challenges. Clin. Exp. Immunol., 2014, 178(Suppl. 1), 30-32.
[http://dx.doi.org/10.1111/cei.12501] [PMID: 25546752]
[13]
Li, H.; Zhai, Z.; Qu, X.; Xu, J.; Qin, A.; Dai, K. MicroRNAs as potential targets for treatment of osteoclast-related diseases. Curr. Drug Targets, 2018, 19(5), 422-431.
[http://dx.doi.org/10.2174/1389450117666160502144329] [PMID: 27138766]
[14]
Lee, C.H.; Kim, J.H.; Lee, S.W. The role of MicroRNA in pathogenesis and as markers of HCV chronic infection. Curr. Drug Targets, 2017, 18(7), 756-765.
[http://dx.doi.org/10.2174/1389450117666160401125213] [PMID: 27033188]
[15]
Hang, P.; Guo, J.; Sun, C.; Du, Z. MicroRNAs as candidate drug targets for cardiovascular diseases. Curr. Drug Targets, 2017, 18(4), 463-472.
[http://dx.doi.org/10.2174/1389450117666160301101221] [PMID: 26926467]
[16]
Rocic, P. Can microRNAs be biomarkers or targets for therapy of ischemic coronary artery disease in metabolic syndrome? Curr. Drug Targets, 2017, 18(15), 1722-1732.
[http://dx.doi.org/10.2174/1389450117666160201113734] [PMID: 26844562]
[17]
Castro, R.E.; Rodrigues, C.M.P. Cell death and microRNAs in cholestatic liver diseases: update on potential therapeutic applications. Curr. Drug Targets, 2017, 18(8), 921-931.
[http://dx.doi.org/10.2174/1389450116666151019102358] [PMID: 26477457]
[18]
Leypoldt, F.; Höftberger, R.; Titulaer, M.J.; Armangue, T.; Gresa-Arribas, N.; Jahn, H.; Rostásy, K.; Schlumberger, W.; Meyer, T.; Wandinger, K.P.; Rosenfeld, M.R.; Graus, F.; Dalmau, J. Investigations on CXCL13 in anti-N-methyl-D-aspartate receptor encephalitis: a potential biomarker of treatment response. JAMA Neurol., 2015, 72(2), 180-186.
[http://dx.doi.org/10.1001/jamaneurol.2014.2956] [PMID: 25436993]
[19]
Zhang, J.; Xu, X.; Zhao, S.; Gong, Z.; Liu, P.; Guan, W.; He, X.; Wang, T.; Peng, T.; Teng, J.; Jia, Y. The expression and significance of the plasma let-7 family in anti-N-methyl-D-aspartate receptor encephalitis. J. Mol. Neurosci., 2015, 56(3), 531-539.
[http://dx.doi.org/10.1007/s12031-015-0489-6] [PMID: 25603816]
[20]
Liba, Z.; Kayserova, J.; Elisak, M.; Marusic, P.; Nohejlova, H.; Hanzalova, J.; Komarek, V.; Sediva, A. Anti-N-methyl-D-aspartate receptor encephalitis: the clinical course in light of the chemokine and cytokine levels in cerebrospinal fluid. J. Neuroinflammation, 2016, 13(1), 55.
[http://dx.doi.org/10.1186/s12974-016-0507-9] [PMID: 26941012]
[21]
Hachiya, Y.; Uruha, A.; Kasai-Yoshida, E.; Shimoda, K.; Satoh-Shirai, I.; Kumada, S.; Kurihara, E.; Suzuki, K.; Ohba, A.; Hamano, S.; Sakuma, H. Rituximab ameliorates anti-N-methyl-D-aspartate receptor encephalitis by removal of short-lived plasmablasts. J. Neuroimmunol., 2013, 265(1-2), 128-130.
[http://dx.doi.org/10.1016/j.jneuroim.2013.09.017] [PMID: 24183642]
[22]
Pham, H.P.; Daniel-Johnson, J.A.; Stotler, B.A.; Stephens, H.; Schwartz, J. Therapeutic plasma exchange for the treatment of anti-NMDA receptor encephalitis. J. Clin. Apher., 2011, 26(6), 320-325.
[http://dx.doi.org/10.1002/jca.20311] [PMID: 21898576]
[23]
Zhong, X.; Wang, H.; Dai, Y.; Wu, A.; Bao, J.; Xu, W.; Cheng, C.; Lu, Z.; Qiu, W.; Hu, X. Cerebrospinal fluid levels of CXCL13 are elevated in neuromyelitis optica. J. Neuroimmunol., 2011, 240-241, 104-108.
[http://dx.doi.org/10.1016/j.jneuroim.2011.10.001] [PMID: 22036953]
[24]
Khademi, M.; Kockum, I.; Andersson, M.L.; Iacobaeus, E.; Brundin, L.; Sellebjerg, F.; Hillert, J.; Piehl, F.; Olsson, T. Cerebrospinal fluid CXCL13 in multiple sclerosis: a suggestive prognostic marker for the disease course. Mult. Scler., 2011, 17(3), 335-343.
[http://dx.doi.org/10.1177/1352458510389102] [PMID: 21135023]
[25]
Karthikeyan, A.; Patnala, R.; Jadhav, S.P.; Eng-Ang, L.; Dheen, S.T. MicroRNAs: key players in microglia and astrocyte mediated inflammation in CNS pathologies. Curr. Med. Chem., 2016, 23(30), 3528-3546.
[http://dx.doi.org/10.2174/0929867323666160814001040] [PMID: 27528056]
[26]
Hsieh, W.J.; Lin, F.M.; Huang, H.D.; Wang, H. Investigating microRNA-target interaction-supported tissues in human cancer tissues based on miRNA and target gene expression profiling. PLoS One, 2014, 9(4)e95697
[http://dx.doi.org/10.1371/journal.pone.0095697] [PMID: 24756070]
[27]
Calin, G.A.; Sevignani, C.; Dumitru, C.D.; Hyslop, T.; Noch, E.; Yendamuri, S.; Shimizu, M.; Rattan, S.; Bullrich, F.; Negrini, M.; Croce, C.M. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc. Natl. Acad. Sci. USA, 2004, 101(9), 2999-3004.
[http://dx.doi.org/10.1073/pnas.0307323101] [PMID: 14973191]
[28]
Beatty, C.W.; Creutzfeldt, C.J.; Davis, A.P.; Hoffer, Z.; Khot, S.P. The diagnostic conundrum and treatment dilemma of a patient with a rapidly progressive encephalopathy. Neurohospitalist, 2014, 4(1), 34-41.
[http://dx.doi.org/10.1177/1941874413496792] [PMID: 24381709]
[29]
Luca, N.; Daengsuwan, T.; Dalmau, J.; Jones, K.; deVeber, G.; Kobayashi, J.; Laxer, R.M.; Benseler, S.M. Anti-N-methyl-D-aspartate receptor encephalitis: a newly recognized inflammatory brain disease in children. Arthritis Rheum., 2011, 63(8), 2516-2522.
[http://dx.doi.org/10.1002/art.30437] [PMID: 21547896]
[30]
Wong-Kisiel, L.C.; Ji, T.; Renaud, D.L.; Kotagal, S.; Patterson, M.C.; Dalmau, J.; Mack, K.J. Response to immunotherapy in a 20-month-old boy with anti-NMDA receptor encephalitis. Neurology, 2010, 74(19), 1550-1551.
[http://dx.doi.org/10.1212/WNL.0b013e3181dd41a1] [PMID: 20458074]
[31]
Marques, I.B.; Teotónio, R.; Cunha, C.; Bento, C.; Sales, F. Anti-NMDA receptor encephalitis presenting with total insomnia--a case report. J. Neurol. Sci., 2014, 336(1-2), 276-280.
[http://dx.doi.org/10.1016/j.jns.2013.10.034] [PMID: 24210076]
[32]
Cantari;n-Extremera, V.; Duat-Rodri;guez, A.; González-Gutiérrez-Solana, L.; López-Mari;n, L.; Armangue, T. Clinical case of anti-N-methyl-D-aspartate receptor encephalitis in an 8-month-old patient with hyperkinetic movement disorder. Pediatr. Neurol., 2013, 48(5), 400-402.
[http://dx.doi.org/10.1016/j.pediatrneurol.2012.12.032] [PMID: 23583060]
[33]
Suzuki, H.; Kitada, M.; Ueno, S.; Tanaka, K.; Kusunoki, S. Anti-NMDAR encephalitis preceded by dura mater lesions. Neurol. Sci., 2013, 34(6), 1021-1022.
[http://dx.doi.org/10.1007/s10072-012-1169-8] [PMID: 22851287]
[34]
Raha, S.; Gadgil, P.; Sankhla, C.; Udani, V. Nonparaneoplastic anti-N-methyl-D-aspartate receptor encephalitis: a case series of four children. Pediatr. Neurol., 2012, 46(4), 246-249.
[http://dx.doi.org/10.1016/j.pediatrneurol.2012.01.012] [PMID: 22490772]
[35]
Takeda, A.; Shimada, H.; Tamura, A.; Yasui, M.; Yamamoto, K.; Itoh, K.; Ataka, S.; Tanaka, S.; Ohsawa, M.; Hatsuta, H.; Hirano, M.; Sakamoto, H.; Ueno, S.; Nakamura, Y.; Tsutada, T.; Miki, T. A case of anti-N-methyl-d-aspartate receptor encephalitis with multiple sclerosis-like demyelinated lesions. Mult. Scler. Relat. Disord., 2014, 3(3), 391-397.
[http://dx.doi.org/10.1016/j.msard.2013.09.005] [PMID: 25876479]
[36]
Aguiar de Sousa, D.; Lobo, P.P.; Caldas, A.C.; Coelho, M.; Albuquerque, L. Pure ataxia associated with N-methyl-D-aspartate receptor antibodies. Parkinsonism Relat. Disord., 2014, 20(5), 568-569.
[http://dx.doi.org/10.1016/j.parkreldis.2014.02.015] [PMID: 24637122]
[37]
Di Capua, D.; Garci;a-Ptacek, S.; Garci;a-Garci;a, M.E.; Abarrategui, B.; Porta-Etessam, J.; Garci;a-Morales, I. Extreme delta brush in a patient with anti-NMDAR encephalitis. Epi. Disord., 2013, 15(4), 461-464.
[http://dx.doi.org/10.1684/epd.2013.0622]
[38]
Ramanathan, S.; Mohammad, S.S.; Brilot, F.; Dale, R.C. Autoimmune encephalitis: recent updates and emerging challenges. J. Clin. Neurosci., 2014, 21(5), 722-730.
[http://dx.doi.org/10.1016/j.jocn.2013.07.017] [PMID: 24246947]
[39]
Dale, R.C.; Pillai, S.; Brilot, F. Cerebrospinal fluid CD19(+) B-cell expansion in N-methyl-D-aspartate receptor encephalitis. Dev. Med. Child Neurol., 2013, 55(2), 191-193.
[http://dx.doi.org/10.1111/dmcn.12036] [PMID: 23151040]
[40]
Finné Lenoir, X.; Sindic, C.; van Pesch, V.; El Sankari, S.; de Tourtchaninoff, M.; Denays, R.; Hantson, P. Anti-N-methyl-D-aspartate receptor encephalitis with favorable outcome despite prolonged status epilepticus. Neurocrit. Care, 2013, 18(1), 89-92.
[http://dx.doi.org/10.1007/s12028-012-9788-8] [PMID: 23090840]
[41]
Shah, R.; Veerapandiyan, A.; Winchester, S.; Gallentine, W.; Mikati, M.A. Two patients with an anti-N-methyl-D-aspartate receptor antibody syndrome-like presentation and negative results of testing for autoantibodies. Pediatr. Neurol., 2011, 45(6), 412-416.
[http://dx.doi.org/10.1016/j.pediatrneurol.2011.09.012] [PMID: 22115008]
[42]
Uruha, A.; Kitazawa, Y.; Kuroda, M.; Tanaka, K.; Koide, R. Anti-NMDAR encephalitis in small-cell lung cancer: a case report. Clin. Neurol. Neurosurg., 2012, 114(3), 260-261.
[http://dx.doi.org/10.1016/j.clineuro.2011.10.015] [PMID: 22047651]
[43]
Frechette, E.S.; Zhou, L.; Galetta, S.L.; Chen, L.; Dalmau, J. Prolonged follow-up and CSF antibody titers in a patient with anti-NMDA receptor encephalitis. Neurology, 2011, 76(7)(Suppl. 2), S64-S66.
[http://dx.doi.org/10.1212/WNL.0b013e31820c34de] [PMID: 21321356]
[44]
Day, G.S.; High, S.M.; Cot, B.; Tang-Wai, D.F. Anti-NMDA-receptor encephalitis: case report and literature review of an under-recognized condition. J. Gen. Intern. Med., 2011, 26(7), 811-816.
[http://dx.doi.org/10.1007/s11606-011-1641-9] [PMID: 21318640]
[45]
Houtrow, A.J.; Bhandal, M.; Pratini, N.R.; Davidson, L.; Neufeld, J.A. The rehabilitation of children with anti-N methyl-D-aspartate-receptor encephalitis: a case series. Am.J.Phys Med Rehabil., 2012, 91(5), 435-441.
[http://dx.doi.org/10.1097/PHM.0b013e3182465da6] [PMID: 22415341]
[46]
Viaccoz, A.; Desestret, V.; Ducray, F.; Picard, G.; Cavillon, G.; Rogemond, V.; Antoine, J.C.; Delattre, J.Y.; Honnorat, J. Clinical specificities of adult male patients with NMDA receptor antibodies encephalitis. Neurology, 2014, 82(7), 556-563.
[http://dx.doi.org/10.1212/WNL.0000000000000126] [PMID: 24443452]
[47]
Liu, J.; Wang, D.; Xiong, Y.; Liu, B.; Liu, M. Anti-NMDAR encephalitis of 11 Cases in China - detailed clinical, laboratory and imagiological description. Eur. Neurol., 2015, 74(1-2), 73-78.
[http://dx.doi.org/10.1159/000435953] [PMID: 26277996]
[48]
Armangue, T.; Moris, G.; Cantari;n-Extremera, V.; Conde, C.E.; Rostasy, K.; Erro, M.E.; Portilla-Cuenca, J.C.; Turón-Viñas, E.; Málaga, I.; Muñoz-Cabello, B.; Torres Torres, C.; Llufriu, S.; González-Gutiérrez-Solana, L.; González, G.; Casado-Naranjo, I.; Rosenfeld, M.; Graus, F.; Dalmau, J. Spanish Prospective Multicentric Study of Autoimmunity in Herpes Simplex Encephalitis. Autoimmune post-herpes simplex encephalitis of adults and teenagers. Neurology, 2015, 85(20), 1736-1743.
[http://dx.doi.org/10.1212/WNL.0000000000002125] [PMID: 26491084]
[49]
DeSena, A.D.; Greenberg, B.M.; Graves, D. Three phenotypes of anti-N-methyl-D-aspartate receptor antibody encephalitis in children: prevalence of symptoms and prognosis. Pediatr. Neurol., 2014, 51(4), 542-549.
[http://dx.doi.org/10.1016/j.pediatrneurol.2014.04.030] [PMID: 25070939]
[50]
Venâncio, P.; Brito, M.J.; Pereira, G.; Vieira, J.P. Anti-N-methyl-D-aspartate receptor encephalitis with positive serum antithyroid antibodies, IgM antibodies against mycoplasma pneumoniae and human herpesvirus 7 PCR in the CSF. Pediatr. Infect. Dis. J., 2014, 33(8), 882-883.
[http://dx.doi.org/10.1097/INF.0000000000000408] [PMID: 25222311]
[51]
Barros, P.; Brito, H.; Ferreira, P.C.; Ramalheira, J.; Lopes, J.; Rangel, R.; Temudo, T.; Figueiroa, S. Resective surgery in the treatment of super-refractory partial status epilepticus secondary to NMDAR antibody encephalitis. Eur. J. Paediatr. Neurol., 2014, 18(3), 449-452.
[http://dx.doi.org/10.1016/j.ejpn.2014.01.013] [PMID: 24594428]
[52]
Tatencloux, S.; Chretien, P.; Rogemond, V.; Honnorat, J.; Tardieu, M.; Deiva, K. Intrathecal treatment of anti-N-Methyl-D-aspartate receptor encephalitis in children. Dev. Med. Child Neurol., 2015, 57(1), 95-99.
[http://dx.doi.org/10.1111/dmcn.12545] [PMID: 25040285]
[53]
Kadoya, M.; Kadoya, A.; Onoue, H.; Ikewaki, K.; Kaida, K. An atypical case of anti-NMDA receptor encephalitis: predominant parkinsonism and persisting micrographia without oro-facial dyskinesia. Intern. Med., 2015, 54(15), 1927-1932.
[http://dx.doi.org/10.2169/internalmedicine.54.3757] [PMID: 26234239]
[54]
Kim, H.; Ryu, H.; Kang, J.K. Anti-NMDA receptor antibody encephalitis presenting with unilateral non-convulsive status epilepticus in a male patient. J. Epilepsy Res., 2015, 5(1), 17-19.
[http://dx.doi.org/10.14581/jer.15004] [PMID: 26157669]
[55]
Loughan, A.R.; Allen, A.; Perna, R.; Malkin, M.G. Anti-N-Methyl-D-Aspartate receptor encephalitis: a review and neuropsychological case study. Clin. Neuropsychol., 2016, 30(1), 150-163.
[http://dx.doi.org/10.1080/13854046.2015.1132772] [PMID: 26998574]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 27
ISSUE: 24
Year: 2020
Page: [4138 - 4151]
Pages: 14
DOI: 10.2174/0929867325666180221142623
Price: $65

Article Metrics

PDF: 33
HTML: 1