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Open Access 24-04-2024 | Anti-NMDA Receptor Encephalitis | Review Article

Perinatal outcome in anti-NMDAr encephalitis during pregnancy—a systematic review with individual patients’ data analysis

Authors: Giovanna Scorrano, Fedele Dono, Clarissa Corniello, Stefano Consoli, Giacomo Evangelista, Armando Di Ludovico, Francesco Chiarelli, Francesca Anzellotti, Angelo Di Iorio, Stefano L. Sensi

Published in: Neurological Sciences

Abstract

Introduction

Anti-N-methyl-D-aspartate receptor (NMDAr) antibody encephalitis is an autoimmune disorder characterized by synaptic NMDAr current disruption and receptor hypofunction, often affecting women during pregnancy. Clinical manifestations associated with anti-NMDAr encephalitis can occur both in the mother and fetus.

Methods

We generated a systematic search of the literature to identify epidemiological, clinical, and serological data related to pregnant women with anti-NMDAr encephalitis and their children, analyzing the fetal outcomes. We examined the age and neurologic symptoms of the mothers, the presence of an underlying tumor, immunotherapies used during pregnancy, duration of the pregnancy, and type of delivery.

Results

Data from 41 patients were extrapolated from the included studies. Spontaneous interruption of pregnancy, premature birth, and cesarean section were reported in pregnant women with NMDAr encephalitis. Several fetal and neonatal symptoms (e.g., movement disorders, spina bifida, poor sucking, respiratory distress, cardiac arrhythmias, infections, icterus, hypoglycemia, and low birth weight) depending on the mother’s serum anti-NR1 concentration were also reported.

Conclusions

We characterized the outcomes of children born from mothers with anti-NMDAr encephalitis, analyzing the pivotal risk factors related to pregnancy and maternal disorder. Neuropsychiatric involvement seems strictly related to pathogenic NMDAr antibodies detected in maternal and/or neonatal serum.

These findings clarify a complex condition to manage, outlining the risks associated with pregnant women with anti-NMDAr encephalitis and also providing a concrete guide for therapeutic strategies to prevent potential harm to the fetus and the child’s neurodevelopment.

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Huang Q, Xie Y, Hu Z, Tang X (2020) Anti-N-methyl-D-aspartate receptor encephalitis: A review of pathogenic mechanisms, treatment, prognosis. Brain Res 1727:146549. https://doi.org/10.1016/j.brainres.2019.146549CrossRefPubMed

Kalam S, Baheerathan A, McNamara C, Singh-Curry V (2019) Anti–NMDAR encephalitis complicating pregnancy. Pract Neurol 19:131–135. https://doi.org/10.1136/practneurol-2018-002042CrossRefPubMed

Liu H, Chen X (2021) Recurrent anti-NMDAR encephalitis during pregnancy combined with two antibodies positive. Arch Womens Ment Health 24:1045–1050. https://doi.org/10.1007/s00737-021-01124-5CrossRefPubMedPubMedCentral

Jurek B, Chayka M, Kreye J, Lang K, Kraus L, Fidzinski P et al (2019) Human gestational N -methyl- D -aspartate receptor autoantibodies impair neonatal murine brain function. Ann Neurol 86:656–670. https://doi.org/10.1002/ana.25552CrossRefPubMed

Lamale-Smith LM, Moore GS, Guntupalli SR, Scott JB (2015) Maternal-fetal transfer of anti–N-methyl-D-aspartate receptor antibodies. Obstet Gynecol 125:1056–1058. https://doi.org/10.1097/AOG.0000000000000548CrossRefPubMed

Jagota P, Vincent A, Bhidayasiri R (2014) Transplacental transfer of NMDA receptor antibodies in an infant with cortical dysplasia. Neurology 82:1662–1663. https://doi.org/10.1212/WNL.0000000000000384CrossRefPubMedPubMedCentral

Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T et al (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15:391–404. https://doi.org/10.1016/S1474-4422(15)00401-9CrossRefPubMedPubMedCentral

Kalam S, Baheerathan A, McNamara C, Singh-Curry V (2019) Anti-NMDAR encephalitis complicating pregnancy. Pract Neurol 19(2):131–135. https://doi.org/10.1136/practneurol-2018-002042CrossRefPubMed

Kim J, Park SH, Jung YR, Park SW, Jung DS (2015) Anti-NMDA receptor encephalitis in a pregnant woman. J Epilepsy Res 5(1):29–32. https://doi.org/10.14581/jer.15008CrossRefPubMedPubMedCentral

10.

Mathis S, Pin JC, Pierre F, Ciron J, Iljicsov A, Lamy M, Neau JP (2015) Anti-NMDA receptor encephalitis during pregnancy: a case report. Medicine 94(26):e1034. https://doi.org/10.1097/MD.0000000000001034CrossRefPubMedPubMedCentral

11.

Chan LW, Nilsson C, Schepel J, Lynch C (2015) A rare case of anti-N-methyl-D-aspartate receptor encephalitis during pregnancy. N Z Med J 128(1411):89–91PubMed

12.

Lamale-Smith LM, Moore GS, Guntupalli SR, Scott JB (2015) Maternal-fetal transfer of anti-N-methyl-D-aspartate receptor antibodies. Obstet Gynecol 125(5):1056–1058. https://doi.org/10.1097/AOG.0000000000000548CrossRefPubMed

13.

Jagota P, Vincent A, Bhidayasiri R (2014) Transplacental transfer of NMDA receptor antibodies in an infant with cortical dysplasia. Neurology 82(18):1662–1663. https://doi.org/10.1212/WNL.0000000000000384CrossRefPubMedPubMedCentral

14.

Lu J, Samson S, Kass J, Ram N (2015) Acute psychosis in a pregnant patient with Graves' hyperthyroidism and anti-NMDA receptor encephalitis. BMJ Case Rep 2015:bcr2014208052. Published 2015 Apr 22. https://doi.org/10.1136/bcr-2014-208052CrossRefPubMedPubMedCentral

15.

Magley J, Towner D, Taché V, Apperson ML (2012) Pregnancy outcome in anti-N-methyl-D-aspartate receptor encephalitis. Obstet Gynecol 120(2 Pt 2):480–483. https://doi.org/10.1097/AOG.0b013e31825935d4CrossRefPubMed

16.

Kumar MA, Jain A, Dechant VE et al (2010) Anti-N-methyl-D-aspartate receptor encephalitis during pregnancy. Arch Neurol 67(7):884–887. https://doi.org/10.1001/archneurol.2010.133CrossRefPubMed

17.

Shahani L (2015) Steroid unresponsive anti-NMDA receptor encephalitis during pregnancy successfully treated with plasmapheresis. BMJ Case Rep 2015:bcr2014208823. Published 2015 Apr 29. https://doi.org/10.1136/bcr-2014-208823CrossRefPubMedPubMedCentral

18.

McCarthy A, Dineen J, McKenna P et al (2012) Anti-NMDA receptor encephalitis with associated catatonia during pregnancy. J Neurol 259(12):2632–2635. https://doi.org/10.1007/s00415-012-6561-zCrossRefPubMed

19.

Ito Y, Abe T, Tomioka R, Komori T, Araki N (2010) Rinsho Shinkeigaku 50(2):103–107. https://doi.org/10.5692/clinicalneurol.50.103CrossRefPubMed

20.

Xiao X, Gui S, Bai P et al (2017) Anti-NMDA-receptor encephalitis during pregnancy: A case report and literature review. J Obstet Gynaecol Res 43(4):768–774. https://doi.org/10.1111/jog.13262CrossRefPubMed

21.

Liu H, Chen X (2021) Recurrent anti-NMDAR encephalitis during pregnancy combined with two antibodies positive. Arch Womens Ment Health 24(6):1045–1050. https://doi.org/10.1007/s00737-021-01124-5CrossRefPubMedPubMedCentral

22.

Joubert B, García-Serra A, Planagumà J, Martínez-Hernandez E, Kraft A, Palm F, Iizuka T, Honnorat J, Leypoldt F, Graus F, Dalmau J (2020) Pregnancy outcomes in anti-NMDA receptor encephalitis: Case series. Neurol Neuroimmunol Neuroinflamm 7(3):e668. https://doi.org/10.1212/NXI.0000000000000668CrossRefPubMedPubMedCentral

23.

Jung KO, Moon HJ (2020 Jun) A case of NMDAR encephalitis treated in the third trimester - novel arterial spin labeling findings and a review of literature. J Neuroimmunol 15(343):577235. https://doi.org/10.1016/j.jneuroim.2020.577235CrossRef

24.

Scorrano G, Dono F, Evangelista G, Chiarelli F, Anzellotti F (2023 Oct) Fetal outcome in anti-NMDAR encephalitis during pregnancy: a case report. Acta Neurol Belg 123(5):1989–1991. https://doi.org/10.1007/s13760-022-02020-0CrossRefPubMed

25.

Demma L, Norris S, Dolak J (2017) Neuraxial anesthesia in a patient with anti-N-methyl-D-aspartate receptor encephalitis in preg- nancy: management for cesarean delivery and oophorectomy. Int J Obstet Anesth 31:104–107. https://doi.org/10.1016/j.ijoa.2017.05.006CrossRefPubMed

26.

Tailland M, Le Verger L, Honnorat J, Biquard F, Codron P, Cassereau J (2020) Post-herpetic anti-N-methyl-d-aspartate receptor encephalitis in a pregnant woman. Rev Neurol (Paris) 176(1–2):129–131. https://doi.org/10.1016/j.neurol.2019.01.402CrossRefPubMed

27.

Lu YT, Hsu CW, Tsai WC, Cheng MY, Shih FY, Fu TY et al (2016) Status epilepticus associated with pregnancy: a cohort study. Epilepsy Behav 59:92–97. https://doi.org/10.1016/j.yebeh.2016.03.034CrossRefPubMed

28.

Chourasia N, Watkins MW, Lankford JE, Kass JS, Kamdar A (2018) An infant born to a mother with anti-N-methyl-d-aspartate re- ceptor encephalitis. Pediatr Neurol 79:65–68. https://doi.org/10.1016/j.pediatrneurol.2017.11.010CrossRefPubMed

29.

Ueda A, Nagao R, Maeda T, Kikuchi K, Murate K, Niimi Y, Shima S, Mutoh T (2017) Absence of serum anti-NMDAR antibodies in anti-NMDAR encephalitis mother predicts having healthy newborn. Clin Neurol Neurosurg 161:14–16. https://doi.org/10.1016/j.clineuro.2017.07.012CrossRefPubMed

30.

Zhang S, Yang Y, Long T, Li Z (2021) Systemic lupus erythematosus associated with recurrent anti-NMDA receptor encephalitis during pregnancy. Arch Womens Ment Health 24(3):525–528. https://doi.org/10.1007/s00737-020-01088-yCrossRefPubMed

31.

Liao Z, Jiang X, Ni J (2017) Anesthesia management of cesarean sec- tion in parturient with anti-N-methyl-D-aspartate receptor encephalitis: a case report. J Anesth 31(2):282–285. https://doi.org/10.1007/s00540-016-2304-0CrossRefPubMed

32.

Kokubun N, Komagamine T, Hirata K (2016) Pregnancy and delivery in anti-NMDA receptor encephalitis survivors. Neurol Clin Pract 6(5):e40–e43. https://doi.org/10.1212/CPJ.0000000000000229CrossRefPubMedPubMedCentral

33.

Mizutamari E, Matsuo Y, Namimoto T, Ohba T, Yamashita Y, Katabuchi H (2016) Successful outcome following detection and removal of a very small ovarian teratoma associated with anti-NMDA receptor encephalitis during pregnancy. Clin Case Rep 4(3):223–225. https://doi.org/10.1002/ccr3.475CrossRefPubMedPubMedCentral

34.

Dono F, Consoli S, Tappatà M, Evangelista G, Russo M, Lanzone J, Pozzilli V, Nucera B, Rinaldi F, Di Pietro M, Tinti L, Troisi S, Calisi D, D'Apolito M, Narducci F, Assenza G, Anzellotti F, Brigo F, Vollono C et al (2023 Dec) Autoimmune encephalitis during pregnancy: A diagnostic and therapeutic challenge-A systematic review with individual patients' analysis and clinical recommendations. Epilepsia Open 8(4):1221–1240. https://doi.org/10.1002/epi4.12806CrossRefPubMedPubMedCentral

35.

Li Y, Meador KJ (2022) Epilepsy and pregnancy. CONTINUUM: Lifelong learning. Neurology 28:34–54. https://doi.org/10.1212/CON.0000000000001056CrossRef

36.

Tomson T, Battino D, Bromley R, Kochen S, Meador K, Pennell P et al (2019) Management of epilepsy in pregnancy: a report from the international league against epilepsy task force on women and pregnancy. Epileptic Disord 21:497–517. https://doi.org/10.1684/epd.2019.1105CrossRefPubMed

37.

Moise AC, Gerard EE (2023) Antiseizure medications in pregnancy. Obstet Gynecol Clin North Am 50:251–261. https://doi.org/10.1016/j.ogc.2022.10.014CrossRefPubMed

38.

Mizutamari E, Matsuo Y, Namimoto T, Ohba T, Yamashita Y, Katabuchi H (2016) Successful outcome following detection and removal of a very small ovarian teratoma associated with anti- NMDA receptor encephalitis during pregnancy. Clin Case Rep 4:223–225. https://doi.org/10.1002/ccr3.475CrossRefPubMedPubMedCentral

39.

Koo F-H, Wang K-C, Chen C-Y, Chang W-H, Yeh C-C, Yang M-J et al (2013) An 11-year experience with ovarian surgery during pregnancy. J Chin Med Assoc 76:452–457. https://doi.org/10.1016/j.jcma.2013.04.008CrossRefPubMed

40.

Demma L, Norris S, Dolak J (2017) Neuraxial anesthesia in a patient with anti-N-methyl-D-aspartate receptor encephalitis in pregnancy: management for cesarean delivery and oophorectomy. Int J Obstet Anesth 31:104–107. https://doi.org/10.1016/j.ijoa.2017.05.006CrossRefPubMed

41.

Reedy MB, Källén B, Kuehl TJ (1997) Laparoscopy during pregnancy: A study of five fetal outcome parameters with use of the Swedish Health Registry. Ame J Obstet Gynecol 177:673–679. https://doi.org/10.1016/S0002-9378(97)70163-7CrossRef

42.

Liao Z, Jiang X, Ni J (2017) Anesthesia management of cesarean section in parturient with anti-N-methyl-d-aspartate receptor encephalitis: a case report. J Anesth 31:282–285. https://doi.org/10.1007/s00540-016-2304-0CrossRefPubMed

Title: Perinatal outcome in anti-NMDAr encephalitis during pregnancy—a systematic review with individual patients’ data analysis
Authors: Giovanna Scorrano
Fedele Dono
Clarissa Corniello
Stefano Consoli
Giacomo Evangelista
Armando Di Ludovico
Francesco Chiarelli
Francesca Anzellotti
Angelo Di Iorio
Stefano L. Sensi
Publication date: 24-04-2024
Publisher: Springer International Publishing
Keywords: Anti-NMDA Receptor Encephalitis
Autoimmune Encephalitis
Levetiracetam
Phenytoin
Status Epilepticus
Epilepsy
Lamotrigine
Published in: Neurological Sciences
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-024-07448-1

At a glance: The STEP trials

Springer Medicine

Perinatal outcome in anti-NMDAr encephalitis during pregnancy—a systematic review with individual patients’ data analysis

Abstract

Introduction

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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