Skip to main content
Log in

Seroprevalence of anti-N-methyl-d-aspartate receptor antibodies in women with ovarian teratoma

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Recently antibodies against neuronal receptors have been identified as cause of a new type of encephalitis. The anti-N-methyl-d-aspartate receptor (anti-NMDA-R) encephalitis is the prototype of these disorders. Patients have a high incidence of teratomata. Removal of teratoma is considered the essential treatment of anti-NMDA-R encephalitis. Here, we aimed to investigate whether neurologically asymptomatic individuals suffering from ovarian teratomata may have positive anti-NMDA-R antibodies to be detected by an established assay. Over a time period of 15 months, all patients suffering from ovarian teratomata without neurological symptoms were included in this prospective study. Twenty consecutive patients were pair matched to patients with other benign ovarian disease and healthy controls. Preoperatively, patients had a gynaecological examination, transvaginal ultrasound, neurological examination and determination of anti-NMDA-R antibodies. None of the patients or controls presented with neurological symptoms. All tumours could be removed completely by laparoscopy. Anti-NMDA-R antibodies were absent in the group of patients with teratomata as well as in patients with benign ovarian tumours and healthy controls. Testing for anti-NMDA-R antibodies revealed negative findings in well-characterised patients with ovarian teratomata lacking neurological symptoms. Our data support the current clinical practice that a systematic screening for anti-NMDA-R antibodies in teratoma patients is not indicated.

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.

Fig. 1

Similar content being viewed by others

References

  1. Dalmau J, Tüzün E, Wu HY, Masjuan J, 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(1):25–36

    Article  PubMed  CAS  Google Scholar 

  2. Tachibana N, Shirakawa T, Ishii K, Takahashi Y, Tanaka K, Arima K, Yoshida T, Ikeda S (2010) Expression of various glutamate receptors including N-methyl-d-aspartate receptor (NMDAR) in an ovarian teratoma removed from a young woman with anti-NMDAR encephalitis. Inter Med 49:2167–2173

    Article  CAS  Google Scholar 

  3. Tüzün E, Zhou L, Baehring JM, Bannykh S, Rosenfeld MR, Dalmau J (2009) Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma. Acta Neuropathol 118(6):737–743

    Article  PubMed  Google Scholar 

  4. Uchino A, Iizuka T, Urano Y, Arai M, Hara A, Hamada J, Hirose R, Dalmau J, Mochizuki H (2011) Pseudo-piano playing motions and nocturnal hypoventilation in anti-NMDA receptor encephalitis: response to prompt tumor removal and immunotherapy. Intern Med 50(6):627–630

    Article  PubMed  CAS  Google Scholar 

  5. Iizuka T, Sakai F, Ide T, Monzen T, Yoshii S, Iigaya M, Suzuki K, Lynch DR, Suzuki N, Hata T, Dalmau J (2008) Anti-NMDA receptor encephalitis in Japan: long-term outcome without tumor removal. Neurology 70(7):504–511

    Article  PubMed  CAS  Google Scholar 

  6. Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R (2011) Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 10(1):63–74 Review

    Article  PubMed  CAS  Google Scholar 

  7. Tumbi A, Gilani A, Scarff JR, Kaur G, Lippmann S (2011) Anti-N-methyl-d encephalitis. Innov Clin Neurosci 8(9):24–25

    PubMed  Google Scholar 

  8. Ryan SA, Costello DJ, Cassidy EM, Brown G, Harrington HJ, Markx S (2013) Anti-NMDA receptor encephalitis: a cause of acute psychosis and catatonia. J Psychiatr Pract 19(2):157–161. doi:10.1097/01.pra.0000428562.86705.cd

    Article  PubMed  Google Scholar 

  9. Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, 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(12):1091–1098

    Article  PubMed  CAS  Google Scholar 

  10. Iizuka T, Yoshii S, Kan S, Hamada J, Dalmau J, Sakai F, Mochizuki H (2010) Reversible brain atrophy in anti-NMDA receptor encephalitis: a long-term observational study. J Neurol 257(10):1686–1691. doi:10.1007/s00415-010-5604-6

    Article  PubMed  Google Scholar 

  11. Sansing LH, Tüzün E, Ko MW, Baccon J, Lynch DR, Dalmau J (2007) A patient with encephalitis associated with NMDA receptor antibodies. Nat Clin Pract Neurol 3(5):291–296

    Article  PubMed  Google Scholar 

  12. Spiegel DR, Zaki N (2013) A case of new onset psychosis in a young woman with minimal response to risperidone, ultimately diagnosed with N-methyl-d-aspartate receptor encephalitis. Clin Schizophr Relat Psychoses:1–20. (Epub ahead of print)

  13. Dericioglu N, Vural A, Acar P, Agayeva N, Ismailova V, Kurne A, Saka E, Arsava EM, Topcuoglu MA (2013) Antiepileptic treatment for anti-NMDA receptor encephalitis: the need for video-EEG monitoring. Epileptic Disord 15(2):166–170. doi:10.1684/epd.2013.0566

    PubMed  Google Scholar 

  14. Wandinger KP, Saschenbrecker S, Stoecker W, Dalmau J (2011) Anti-NMDA-receptor encephalitis: a severe, multistage, treatable disorder presenting with psychosis. J Neuroimmunol 231(1–2):86–91

    Article  PubMed  CAS  Google Scholar 

  15. Prüss H, Dalmau J, Arolt V, Wandinger K-P (2010) Anti-NMDA-Rezeptor-Enzephalitis. Ein interdisziplinäres Krankheitsbild. Nervenarzt 81:396–408

    Article  PubMed  Google Scholar 

  16. Boeck AL, Logemann F, Krauß T, Hussein K, Bültmann E, Trebst C, Stangel M (2013) Ovarectomy despite negative imaging in anti-NMDA receptor encephalitis: effective even late. Case Rep Neurol Med 2013:843192. doi:10.1155/2013/843192

    PubMed  Google Scholar 

  17. Batra R, Pang Y, Friedman MT (2012) Therapeutic plasma exchange in anti-N-methyl-d-aspartate-receptor (anti-NMDA-R) encephalitis associated with benign ovarian teratoma. J Clin Apher 27(4):227–228. doi:10.1002/jca.21212 No abstract available

    Article  PubMed  Google Scholar 

  18. Kitada M, Suzuki H, Ichihashi J, Mitsui Y, Tanaka K, Kusunoki S (2011) Dramatic improvement in two cases of anti-NMDA receptor encephalitis after immunomodulating therapy. Rinsho Shinkeigaku 51(9):683–687 Japanese

    Article  PubMed  Google Scholar 

  19. Peery HE, Day GS, Dunn S, Fritzler MJ, Prüss H, De Souza C, Doja A, Mossman K, Resch L, Xia C, Sakic B, Belbeck L, Foster WG (2012) Anti-NMDA receptor encephalitis. The disorder, the diagnosis and the immunobiology. Autoimmun Rev 11:863–872

    Article  PubMed  CAS  Google Scholar 

  20. Wandinger KP, Klingbeil C, Gneiss C, Waters P, Dalmau J, Saschenbrecker S, Borowski K, Deisenhammer F, Vincent A, Probst C, Stöcker W () New serological markers for the differential diagnosis of autoimmune limbic encephalitis. Laboratoriumsmedizin. Band 0, Heft 0, Seiten, ISSN (online) 1439-0477, ISSN (print) 0342-3026. doi:10.1515/jlm.2011.059et

  21. Stöcker W, Saschenbrecker S, Rentzsch K, Komorowski L, Probst C (2013) Autoantikörperdiagnostik in der Neurologie mittels nativer und rekombinanter Antigensubstrate. Der Nervenarzt 84(4):471–476

    Article  PubMed  Google Scholar 

  22. Martinez-Hernandez E, Horvath J, Shiloh-Malawsky Y, Sangha N, Martinez-Lage M, Dalmau J (2011) Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis. Neurology 77:589–593

    Article  PubMed  CAS  Google Scholar 

  23. Titulaer MJ, Kayser MS, Dalmau J (2013) Prevalence and treatment of anti-NMDA receptor encephalitis—authors’ reply. Lancet Neurol 12:425–426

    Article  PubMed  Google Scholar 

  24. Irani SR, Bera K, Waters P et al (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

    Article  PubMed  Google Scholar 

  25. Steiner J, Walter M, Glanz W et al (2013) Increased prevalence of diverse N-methyl-d-aspartate glutamate receptor antibodies in patients with an initial diagnosis of schizophrenia: specific relevance of IgG NR1a antibodies for distinction from N-methyl-d-aspartate glutamate receptor encephalitis. JAMA psychiatry 70(3):271–278. doi:10.1001/2013.jamapsychiatry.86

  26. Prüss H, Finke C, Höltje M et al (2012) N-methyl-d-aspartate receptor antibodies in herpes simplex encephalitis. Ann Neurol 72(6):902–911. doi:10.1002/ana.23689

    Article  PubMed  Google Scholar 

  27. Prüss H, Dalmau J, Harms L, Höltje M, Ahnert-Hilger G, Borowski K, Stoecker W, Wandinger KP (2010) Retrospective analysis of NMDA receptor antibodies in encephalitis of unknown origin. Neurology 75(19):1735–1739

    Article  PubMed  Google Scholar 

  28. Ella Wotzke Dissertation an der Rheinischen Friedrich-Wilhelms-Universität Bonn “Häufigkeit und Phänotyp neurologischer und psychiatrischer Symptome bei Patientinnen mit ovariellen Teratomen: Eine Fragebogenstudie”. http://hss.ulb.uni-bonn.de/2011/2449/2449.pdf

  29. Niehusmann P, Dalmau J, Rudlowski C, Vincent A, Elger CE, Rossi JE, Bien C (2009) Diagnostic value of N-methyl-d-aspartate receptor antibodies in women with new-onset epilepsy. Arch Neurol 66(4):458–464. doi:10.1001/archneurol.2009.5

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Julia Lange very much for providing the ultrasound picture of a teratoma. We would also like to thank Barbara Ingold-Heppner very much for kindly preparing the pathological figure.

Conflicts of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mandy Mangler.

Electronic supplementary material

Below is the link to the electronic supplementary material.

415_2013_7074_Fig2_ESM.jpg

Typical ultrasound picture of ovarian teratoma 8.9 cm in size (provided by Dr. Julia Lange, Praxis Kurfürstendamm 199, 10719 Berlin) (JPEG 140 kb)

Histopathological pictures of teratoma in 500 μm solution (JPEG 280 kb)

Histopathological pictures of teratoma in 200 μm solution (JPEG 292 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mangler, M., Trebesch de Perez, I., Teegen, B. et al. Seroprevalence of anti-N-methyl-d-aspartate receptor antibodies in women with ovarian teratoma. J Neurol 260, 2831–2835 (2013). https://doi.org/10.1007/s00415-013-7074-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-013-7074-0

Keywords

Navigation