Surgical outcomes in patients with anti-N-methyl D-aspartate receptor encephalitis with ovarian teratoma


      Anti–N-methyl-D-aspartate receptor encephalitis is an autoimmune encephalitis mediated by anti–N-methyl-D-aspartate receptor antibodies. Ovarian teratoma is closely related to anti–N-methyl-D-aspartate receptor encephalitis. However, the optimal treatment remains unknown, and strategies used for the diagnosis and therapy, including surgical intervention of ovarian teratoma, are debatable.


      The objective of the study was to study the clinical features of anti–N-methyl-D-aspartate receptor encephalitis with ovarian teratoma to further understand the disease.

      Study Design

      This single-center prospective study included patients with anti-NMDAR encephalitis with ovarian teratoma from 2011 to 2016 who were admitted to Peking Union Medical College Hospital, Beijing, and discussed the clinical characteristics, treatment, and prognosis of the disease. The diagnosis of anti–N-methyl-D-aspartate receptor encephalitis was established preoperatively by identifying anti–N-methyl-D-aspartate receptor antibodies in the cerebrospinal fluid. Ovarian teratomas were suspected preoperatively by pelvic ultrasound and were diagnosed pathologically after laparoscopic detection and ovarian tumor resection. All patients were treated with first-line immunotherapy (steroids, intravenous immunoglobulin, and plasmapheresis), and when the therapy failed, they were treated with second-line immunotherapy (cyclophosphamide and rituximab). All patients were followed up regularly, and N-methyl-D-aspartate receptor antibodies, pelvic ultrasound, and neurological condition were monitored. Neurological symptoms were assessed using the modified Rankin Scale.


      A total of 108 female patients with anti–N-methyl-D-aspartate receptor encephalitis were screened, of whom, 29 patients (26.9% of 108; mean age ± SD, 23.14 ± 6.59 years) had pathologically confirmed ovarian teratoma. The incidence of fever, decreased consciousness, arrhythmia, central hypoventilation, ventilator-assisted respiration, and intensive unit care (75.9%, 65.5%, 27.6%, 55.2%, 55.2%, and 58.6%, respectively) were significantly higher in patients with ovarian teratoma than in those without ovarian teratoma. The modified Rankin Scale at the acute onset in those 29 patients was 4.11 ± 1.20, which was also much higher than that in patients without ovarian teratoma (3.58 ± 1.08). Of the 29 patients with ovarian teratoma, 22 (75.9%) underwent laparoscopy during the acute onset of neurological symptoms. The mean diameter of the tumor was 4.61 ± 3.41 cm (SD), and the smallest tumor was only 1 cm in the unilateral ovary. All other cysts, except 4 bilateral cysts (13.8%), were unilateral. Only 1 patient was diagnosed pathologically with immature ovarian teratoma, while others had benign ovarian teratomas. In all, 28 patients (96.5%) had a good outcome (modified Rankin Scale ≤2) and 1 died. In the follow-up visit (mean duration, 37.69 months), the relapse rate of encephalitis in patients with ovarian teratoma undergoing laparoscopic cystectomy was 14.6%, whereas for those without ovarian teratoma, the relapse rate was 33.3%. The removal of ovarian teratoma was associated with reduced risk of relapse.


      Patients having anti–N-methyl-D-aspartate receptor encephalitis with ovarian teratomas tend to present more severe neurological conditions. The diameter of the tumor in these patients is not very large and could be as small as 1 cm, and thus, careful exploration should be considered during surgery. Most of the ovarian teratomas in patients with anti–N-methyl-D-aspartate receptor encephalitis are mature. Early operative treatment is safe and effective because it is associated with reduced risk of relapse and complete recovery.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Dalmau J.
        • Tüzün E.
        • Wu H.
        • et al.
        Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma.
        Ann Neurol. 2007; 61: 25-36
        • Barry H.
        • Byrne S.
        • Barrett E.
        • Murphy K.C.
        • Cotter D.R.
        Anti-N-methyl-d-aspartate receptor encephalitis: review of clinical presentation, diagnosis and treatment.
        Br J Psychol Bull. 2015; 39: 19-23
        • Abe K.K.
        • Koli R.L.
        • Yamamoto L.G.
        Emergency department presentations of anti-N-methyl-D-aspartate receptor encephalitis.
        Pediatr Emerg Care. 2016; 32 (quiz 113-15): 107-112
        • Yang X.-Z.
        • Cui L.-Y.
        • Ren H.-T.
        • Qu T.
        • Guan H.-Z.
        Anti-NMDAR encephalitis after resection of melanocytic nevi: report of two cases.
        BMC Neurol. 2015; 15: 165
        • Yao Y.
        • Peng B.
        • Wang X.H.
        • et al.
        [Analysis of prodromal phase and prodromal events in anti-N-methyl-D-aspartate receptor encephalitis].
        Zhonghua Yi Xue Za Zhi. 2017; 97: 1469-1473
        • Yin H.
        • Zhu C.
        • Ren H.
        • et al.
        Resection of melanocytic nevi as a potential treatment of anti-NMDAR encephalitis patients without tumor: report of three cases.
        Neurol Sci. 2018; 39: 165-167
        • Yang X.-Z.
        • Zhu H.-D.
        • Ren H.-T.
        • et al.
        Utility and safety of intrathecal methotrexate treatment in severe anti-N-methyl-D-aspartate receptor encephalitis: a pilot study.
        Chin Med J. 2018; 131: 156-160
        • Wang R.
        • Guan H.-Z.
        • Ren H.-T.
        • Wang W.
        • Hong Z.
        • Zhou D.
        CSF findings in patients with anti-N-methyl-D-aspartate receptor-encephalitis.
        Seizure. 2015; 29: 137-142
        • Gong Y.-H.
        • Zhang M.-Z.
        • Zhang X.-H.
        • Guan H.-Z.
        • Xu X.-Q.
        • Huang Y.-G.
        Potential effect of preoperative immunotherapy on anesthesia of patients with anti-N-methyl-D-aspartate receptor encephalitis.
        Chin Med J. 2015; 128: 2972-2975
        • Yuan J.
        • Guan H.
        • Zhou X.
        • et al.
        Changing brain metabolism patterns in patients with ANMDARE: serial 18F-FDG PET/CT findings.
        Clin Nucl Med. 2016; 41: 366-370
        • Yuan J.
        • Peng B.
        • Guan H.Z.
        • et al.
        [Immunotherapy strategy for 35 cases of severe anti-N-methyl-D-aspartate receptor encephalitis].
        Zhonghua Yi Xue Za Zhi. 2016; 96: 1035-1039
        • Zhou X.
        • Sun D.
        • Feng L.
        • et al.
        [Ovarian teratoma associated with anti-N-methyl-D-aspartate receptor encephalitis: a report of 5 cases and review of the literature].
        Zhonghua Fu Chan Ke Za Zhi. 2014; 49: 281-286
        • Graus F.
        • Titulaer M.J.
        • Balu R.
        • et al.
        A clinical approach to diagnosis of autoimmune encephalitis.
        Lancet Neurol. 2016; 15: 391-404
        • Titulaer M.J.
        • McCracken L.
        • Gabilondo I.
        • et al.
        Treatment and prognostic factors for long-term outcome in patients with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis: a cohort study.
        Lancet Neurol. 2013; 12: 157-165
        • Gresa-Arribas N.
        • Titulaer M.J.
        • Torrents A.
        • et al.
        Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study.
        Lancet Neurol. 2014; 13: 167-177
        • Titulaer M.J.
        • 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: 157-165
        • Florance N.R.
        • Davis R.L.
        • Lam C.
        • et al.
        Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents.
        Ann Neurol. 2009; 66: 11-18
        • Li X.M.
        • Jiang H.Y.
        • Wang Y.F.
        • Qiu W.
        • Wang Y.
        • Wu H.T.
        [Ovarian tumor associated with anti-N-methyl-D-aspartate receptor encephalitis: a report of 15 cases].
        Zhonghua Yi Xue Za Zhi. 2017; 97: 2932-2935
        • Leel N.
        • Thakkar H.S.
        • Drake D.
        • Bouhadiba N.
        Ovarian teratoma associated with anti-NMDA (N-methyl D-aspartate) receptor encephalitis.
        BMJ Case Rep. 2018; 2018
        • Lesher A.P.
        • Myers T.J.
        • Tecklenburg F.
        • Streck C.J.
        Anti–N-methyl-d-aspartate receptor encephalitis associated with an ovarian teratoma in an adolescent female.
        J Pediatr Surg. 2010; 45: 1550-1553
        • Zaborowski M.P.
        • Spaczynski M.
        • Nowak-Markwitz E.
        • Michalak S.
        Paraneoplastic neurological syndromes associated with ovarian tumors.
        J Cancer Res Clin Oncol. 2015; 141: 99-108
        • Tanyi J.L.
        • Marsh E.B.
        • Dalmau J.
        • Chu C.S.
        Reversible paraneoplastic encephalitis in three patients with ovarian neoplasms.
        Acta Obstet Gynecol Scand. 2012; 91: 630-634
        • Iemura Y.
        • Yamada Y.
        • Hirata M.
        • Kataoka T.R.
        • Minamiguchi S.
        • Haga H.
        Histopathological characterization of the neuroglial tissue in ovarian teratoma associated with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis.
        Pathol Int. 2018; 68: 677-684
        • Day G.S.
        • Laiq S.
        • Tang-Wai D.F.
        • Munoz D.G.
        Abnormal neurons in teratomas in NMDAR encephalitis.
        JAMA Neurol. 2014; 71: 717-724
        • Tabata E.
        • Masuda M.
        • Eriguchi M.
        • et al.
        Immunopathological significance of ovarian teratoma in patients with anti-N-methyl-d-aspartate receptor encephalitis.
        Eur Neurol. 2014; 71: 42-48
        • Mizutamari E.
        • Matsuo Y.
        • Namimoto T.
        • Ohba T.
        • Yamashita Y.
        • Katabuchi H.
        Successful outcome following detection and removal of a very small ovarian teratoma associated with anti-NMDA receptor encephalitis during pregnancy.
        Clin Case Rep. 2016; 4: 223-225
        • Bost C.
        • Chanson E.
        • Picard G.
        • et al.
        Malignant tumors in autoimmune encephalitis with anti-NMDA receptor antibodies.
        J Neurol. 2018; 265: 2190-2200
        • Guan H.-Z.
        • Ren H.-T.
        • Cui L.-Y.
        Autoimmune encephalitis: an expanding frontier of neuroimmunology.
        Chin Med J. 2016; 129: 1122-1127
        • Mooneyham G.C.
        • Gallentine W.
        • Van Mater H.
        Evaluation and management of autoimmune encephalitis: a clinical overview for the practicing child psychiatrist.
        Child Adolesc Psychiatr Clin N Am. 2018; 27: 37-52
        • Liang Z.
        • Yang S.
        • Sun X.
        • et al.
        Teratoma-associated anti-NMDAR encephalitis: two cases report and literature review.
        Medicine (Baltimore). 2017; 96: e9177
        • Kleinig T.J.
        • Thompson P.D.
        • Matar W.
        • et al.
        The distinctive movement disorder of ovarian teratoma-associated encephalitis.
        Mov Disord. 2008; 23: 1256-1261
        • Mitra A.D.
        • Afify A.
        Ovarian teratoma associated anti-N-methyl-D-aspartate receptor encephalitis: a difficult diagnosis with a favorable prognosis.
        Autops Case Rep. 2018; 8: e2018019
        • Ahmad J.
        • Sohail M.S.
        • Khan A.
        • et al.
        Anti-n-methyl-d-aspartate-receptor (NMDAR) encephalitis in association with ovarian teratoma.
        Cureus. 2017; 9: e1425