Abstract
Objective
The aim of this study was to describe specificities of patients with NMDA receptor antibody (NMDAR-Ab) encephalitis associated with a malignant tumor.
Methods
Retrospective observational study of 252 patients with NMDAR-Ab encephalitis of the French Paraneoplastic Neurological Syndrome Reference Center. Patients were classified in three groups: (1) non-malignant ovarian teratomas, (2) malignant ovarian teratomas (immature), and (3) other malignant tumors.
Results
Sixty patients (23.8%) had an associated tumor and 15 (6%) were malignant. No particular neurological symptom was observed in these patients. Ovarian teratomas were the most frequent (51 cases) with 6 of them immature (11.8% of teratomas). Nine patients (3.6%) developed other malignant tumors (3 small cell lung carcinomas, 1 uterine adenocarcinoma, 1 prostate adenocarcinoma, 1 Hodgkin lymphoma, 1 pineal dysgerminoma, 1 neuroblastoma and 1 pancreatic neuroendocrine tumor). Among patients with a cancer other than teratoma, 6/9 were elderly patients (median age 65 years, representing 30% of elderly patients with such encephalitis) compared to a median age of 26 years in adult patients included herein. The clinical course was similar in the three groups, other than a higher death rate among patients with malignant tumors (86 versus 2%; p < 0.001) mainly due to tumor progression (5/7 deaths).
Conclusion
Immature ovarian teratomas represent 11.8% of all teratomas in patients with NDMAR-Ab encephalitis. The other malignant tumors are mainly observed in elderly patients. The presence of a malignant tumor does not impact the neurological presentation but is directly associated with a higher risk of death.
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References
Graus F, Titulaer MJ, Balu R et al (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15(4):391–404
Vitaliani R, Mason W, Ances B et al (2005) Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma. Ann Neurol 58(4):594–604
Dalmau J, Tüzün E, Wu HY et al (2007) Paraneoplastic anti-N-methyl-d-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 61(1):25–36
Dalmau J, Gleichman AJ, Hughes EG et al (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7(12):1091–1098
Titulaer MJ, Mccracken L, Gabilondo I et al (2013) Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 12(2):157–165
Lim J-A, Lee S-T, Jung K-H et al (2014) Anti-N-methyl-d-aspartate receptor encephalitis in Korea: clinical features, treatment, and outcome. J Clin Neurol 10(2):157–161
Gresa-Arribas N, Titulaer MJ, Torrents A et al (2014) Diagnosis and significance of antibody titers in anti-NMDA receptor encephalitis, a retrospective study. Lancet Neurol 13(2):167–177
Viaccoz A, Desestret V, Ducray F et al (2014) Clinical specificities of adult male patients with NMDA receptor antibodies encephalitis. Neurology 82(7):556–563
Zekeridou A, Karantoni E, Viaccoz A et al (2015) Treatment and outcome of children and adolescents with N-methyl-d-aspartate receptor encephalitis. J Neurol 262(8):1859–1866
Dalmau J, Lancaster E, Martinez-Hernandez E,et al (2011) Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 10(1):63–74
Afanasiev V, Brechemier M-L, Boisseau W et al (2016) Anti-NMDA receptor antibody encephalitis and neuroendocrine pancreatic tumor: causal link? Neurology 87(1):112–113
Lebas A, Husson B, Didelot A et al (2010) Expanding spectrum of encephalitis with NMDA receptor antibodies in young children. J Child Neurol 25(6):742–745
Tüzün E, Zhou L, Baehring JM et al (2009) Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma. Acta Neuropathol 118(6):737–743
Dabner M, McCluggage WG, Bundell C et al (2012) Ovarian teratoma associated with anti-N-methyl d-aspartate receptor encephalitis: a report of 5 cases documenting prominent intratumoral lymphoid infiltrates. Int J Gynecol Pathol 31(5):429–437
Outwater EK, Siegelman ES, Hunt JL (2001) Ovarian teratomas: tumor types and imaging characteristics. Radiographics 21(2):475–490
Shaaban AM, Rezvani M, Elsayes KM et al (2014) Ovarian malignant germ cell tumors: cellular classification and clinical and imaging features. RadioGraphics 34(3):777–801
Terenziani M, D’Angelo P, Inserra A et al (2015) Mature and immature teratoma: a report from the second Italian pediatric study. Pediatr Blood Cancer 62(7):1202–1208
Wagner U, Harter P, Hilpert F et al (2013) S3-guideline on diagnostics, therapy and follow-up of malignant ovarian tumours: short version 1.0. Geburtshilfe Frauenheilkd 73(9):874–889
Coban A, Gundogdu G, Poyraz M et al (2016) NMDA receptor encephalitis with cancer of unknown primary origin. Tumori 102(Suppl 2):S3–4
Jeraiby M, Depincé-Berger A, Bossy V et al (2016) A case of anti-NMDA receptor encephalitis in a woman with a NMDA-R + small cell lung carcinoma (SCLC). Clin Immunol 166–167:96–99
Wu YY, He XJ, Zhang ML, Shi YY, Zhang JW (2016) Anti-N-methyl-d-aspartate receptor encephalitis with lung adenocarcinoma. Neurol Sci 37(9):1573–1575
Hara M, Morita A, Kamei S et al (2011) Anti-N-methyl-d-aspartate receptor encephalitis associated with carcinosarcoma with neuroendocrine differentiation of the uterus. J Neurol 258(7):1351–1353
Hattori Y, Yamashita Y, Mizuno M et al (2017) Anti-N-methyl-d-aspartate receptor limbic encephalitis associated with mature cystic teratoma of the fallopian tube. J Obstet Gynaecol Res 43(2):412–415
Williams TJ, Benavides DR, Patrice K-A et al (2016) Association of autoimmune encephalitis with combined immune checkpoint inhibitor treatment for metastatic cancer. JAMA Neurol 73(8):928
Ding L, Tan H, Li Z et al (2017) Case report: anaesthetic management of radical gastrectomy for gastric cancer associated with anti-N-methyl-d-aspartate receptor encephalitis. BMC Anesthesiol 17(1):1–5
Lim EW, Yip CW (2017) Anti-N-methyl-d-aspartate receptor encephalitis associated with hepatic neuroendocrine carcinoma: a case report. J Clin Neurosci 41:70–72
Zandi MS, Irani SR, Follows G et al (2009) Limbic encephalitis associated with antibodies to the NMDA receptor in Hodgkin lymphoma. Neurology 73(23):2039–2040
Graus F, Delattre JY, Antoine J-C et al (2004) Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 75:1135–1141
Acknowledgements
We gratefully thank Dr Lara Chalabreysse and Dr Isabelle Treilleux for the helpful collaboration. This study was supported by research Grants from Agence Nationale de la Recherche (ANR-14-CE15-0001-MECANO), the Fondation pour la recherche sur le cerveau (FRC-Neurodon2014) and CSL Behring France, FRM (Fondation pour la recherche médicale) DQ20170336751.
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Dr Chloé Bost: analysis, interpretation of the data, drafting the manuscript for intellectual content. Dr Eve Chanson: analysis, interpretation of the data, drafting the manuscript for intellectual content. Ms Géraldine Picard: acquisition and analysis of data. Dr David Meyronet: acquisition and analysis of data. Ms Marie-Eve Mayeur: acquisition and analysis of data. Dr François Ducray: acquisition of data, critical revision of the manuscript for important intellectual content. Dr Véronique Rogemond: acquisition and analysis of data. Dr Dimitri Psimaras: acquisition of data, critical revision of the manuscript for important intellectual content. Pr Jean-Christophe Antoine: acquisition of data, critical revision of the manuscript for important intellectual content. Pr Jean-Yves Delattre: critical revision of the manuscript for important intellectual content. Dr Virginie Desestret: analysis and interpretation, critical revision of the manuscript for important intellectual content, study supervision. Pr Jérôme Honnorat: study concept and design, analysis and interpretation, critical revision of the manuscript for important intellectual content, study supervision.
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This study is not industry-sponsored. Dr Chloé Bost reports no disclosures; Dr Eve Chanson reports no disclosures; Ms Géraldine Picard reports no disclosures; Dr David Meyronet reports no disclosures; Ms Marie-Eve Mayeur reports no disclosures; Dr François Ducray reports no disclosures; Dr Véronique Rogemond reports no disclosures; Dr Dimitri Psimaras and Pr Jean-Christophe Antoine report no disclosures; Pr Jean-Yves Delattre reports no disclosures; Dr Virginie Desestret reports no disclosures; Pr Jérôme Honnorat reports no disclosures.
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Written consent was obtained from all patients, and this study was approved by the institutional review board of the University Claude Bernard Lyon 1 and Hospices Civils de Lyon.
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Bost, C., Chanson, E., Picard, G. et al. Malignant tumors in autoimmune encephalitis with anti-NMDA receptor antibodies. J Neurol 265, 2190–2200 (2018). https://doi.org/10.1007/s00415-018-8970-0
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DOI: https://doi.org/10.1007/s00415-018-8970-0