Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis | Adolescent Medicine | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody EncephalitisA Meta-analysis

Educational Objective
To investigate the most effective treatments for N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis.
1 Credit CME
Key Points

Question  What are the most effective treatments for N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis?

Findings  In this meta-analysis of individual patient data including 1550 cases, treatment factors at first event that were significantly associated with good functional outcome 12 months from disease onset included first-line treatment with therapeutic apheresis alone, corticosteroids in combination with intravenous immunoglobulin (IVIG), or corticosteroids in combination with IVIG and therapeutic apheresis, while lack of immunotherapy within 30 days of disease onset was significantly associated with poor outcome. Rituximab and long-term IVIG use were significantly associated with nonrelapsing disease course.

Meaning  Separate treatment factors are associated with functional outcomes and relapsing disease biology in those with NMDAR antibody encephalitis.

Abstract

Importance  Overall, immunotherapy has been shown to improve outcomes and reduce relapses in individuals with N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis (NMDARE); however, the superiority of specific treatments and combinations remains unclear.

Objective  To map the use and safety of immunotherapies in individuals with NMDARE, identify early predictors of poor functional outcome and relapse, evaluate changes in immunotherapy use and disease outcome over the 14 years since first reports of NMDARE, and assess the Anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score.

Data Sources  Systematic search in PubMed from inception to January 1, 2019.

Study Selection  Published articles including patients with NMDARE with positive NMDAR antibodies and available individual immunotherapy data.

Data Extraction and Synthesis  Individual patient data on immunotherapies, clinical characteristics at presentation, disease course, and final functional outcome (modified Rankin Scale [mRS] score) were entered into multivariable logistic regression models.

Main Outcomes and Measures  The planned study outcomes were functional outcome at 12 months from disease onset (good, mRS score of 0 to 2; poor, mRS score greater than 2) and monophasic course (absence of relapse at 24 months or later from onset).

Results  Data from 1550 patients from 652 articles were evaluated. Of these, 1105 of 1508 (73.3%) were female and 707 of 1526 (46.3%) were 18 years or younger at disease onset. Factors at first event that were significantly associated with good functional outcome included adolescent age and first-line treatment with therapeutic apheresis, corticosteroids plus intravenous immunoglobulin (IVIG), or corticosteroids plus IVIG plus therapeutic apheresis. Factors significantly associated with poor functional outcome were age younger than 2 years or age of 65 years or older at onset, intensive care unit admission, extreme delta brush pattern on electroencephalography, lack of immunotherapy within the first 30 days of onset, and maintenance IVIG use for 6 months or more. Factors significantly associated with nonrelapsing disease were rituximab use or maintenance IVIG use for 6 months or more. Adolescent age at onset was significantly associated with relapsing disease. Rituximab use increased from 13.5% (52 of 384; 2007 to 2013) to 28.3% (311 of 1100; 2013 to 2019) (P < .001), concurrent with a falling relapse rate over the same period (22% [12 of 55] in 2008 and earlier; 10.9% [35 of 322] in 2017 and later; P = .006). Modified NEOS score (including 4 of 5 original NEOS items) was associated with probability of poor functional status at 1 year (20.1% [40 of 199] for a score of 0 to 1 points; 43.8% [77 of 176] for a score of 3 to 4 points; P = .05).

Conclusions and Relevance  Factors influencing functional outcomes and relapse are different and need to be considered independently in development of evidence-based optimal management guidelines of patients with NMDARE.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: July 30, 2021.

Published Online: September 20, 2021. doi:10.1001/jamaneurol.2021.3188

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Nosadini M et al. JAMA Neurology.

Corresponding Author: Ming Lim, MD, PhD, Children’s Neurosciences, Evelina London Children’s Hospital at Guy’s and St Thomas’ NHS Foundation Trust, Westminster Bridge Road, London SE1 7EH, United Kingdom (ming.lim@gstt.nhs.uk).

The International NMDAR Antibody Encephalitis Consensus Group: Banu Anlar, MD; Thaís Armangue, MD, PhD; Susanne Benseler, MD; Tania Cellucci, MD, MScCH; Kumaran Deiva, MD; William Gallentine, DO; Grace Gombolay, MD; Mark P. Gorman, MD; Yael Hacohen, MD, PhD; Yuwu Jiang, MD; Byung Chan Lim, MD; Eyal Muscal, MD, MS; Alvin Ndondo, MD; Rinze Neuteboom, MD, PhD; Kevin Rostásy, MD; Hiroshi Sakuma, MD; Stefano Sartori, MD, PhD; Suvasini Sharma, MD; Silvia Noemi Tenembaum, MD; Heather Ann Van Mater, MD; Elizabeth Wells, MD; Ronny Wickstrom, MD, PhD; Anusha K. Yeshokumar, MD.

Affiliations of The International NMDAR Antibody Encephalitis Consensus Group: Neuroimmunology Group, Paediatric Research Institute “Città della Speranza,” Padova, Italy (Sartori); Neuroimmunology Program, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain (Armangue); Hacettepe University, Ankara, Turkey (Anlar); Sant Joan de Déu (SJD) Children’s Hospital, University of Barcelona, Barcelona, Spain (Armangue); Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada (Benseler); McMaster University, Hamilton, Ontario, Canada (Cellucci); Assistance Publique-Hôpitaux de Paris, University Hospitals Paris Saclay, Bicêtre Hospital, Paris, France (Deiva); French Reference Network of Rare Inflammatory Brain and Spinal Diseases, Paris, France (Deiva); European Reference Network-RITA, Paris, France (Deiva); Stanford University and Lucile Packard Children’s Hospital, Palo Alto, California (Gallentine); Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia (Gombolay); Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts (Gorman); Queen Square MS Centre, UCL Institute of Neurology, University College London, London, United Kingdom (Hacohen); Department of Paediatric Neurology, Great Ormond Street Hospital for Children, London, United Kingdom (Hacohen); Peking University First Hospital, Beijing, China (Jiang); Pediatric Clinical Neuroscience Center, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea (Lim); Section Rheumatology, Texas Children’s Hospital, Baylor College of Medicine, Houston (Muscal); Child Health, Red Cross War Memorial Children’s Hospital, University of Cape Town, Cape Town, South Africa (Ndondo); Faculty of Health Sciences, University of Cape Town Neuroscience Institute, Cape Town, South Africa (Ndondo); Erasmus Medical Center, Rotterdam, the Netherlands (Neuteboom); Children’s Hospital Datteln, University Witten/Herdecke, Witten, Germany (Rostásy); Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan (Sakuma); University Hospital of Padova, Padova, Italy (Sartori); Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, New Delhi, India (Sharma); National Pediatric Hospital Dr J. Garrahan, Buenos Aires, Argentina (Tenembaum); Duke University, Durham, North Carolina (Van Mater); Children’s National Medical Center, Washington, DC (Wells); Karolinska University Hospital, Stockholm, Sweden (Wickstrom); Icahn School of Medicine at Mount Sinai, New York, New York (Yeshokumar).

Author Contributions: Drs Nosadini and M. Lim had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Nosadini and Eyre contributed equally to this work.

Study concept and design: Nosadini, Eyre, Molteni, Dale, M. Lim, Anlar, Ndondo, Sartori, Sharma.

Acquisition, analysis, or interpretation of data: Nosadini, Eyre, Molteni, Thomas, Irani, Dalmau, Dale, M. Lim, Armangue, Benseler, Cellucci, Deiva, Gallentine, Gombolay, Gorman, Hacohen, Jiang, B. Lim, Muscal, Neuteboom, Rostásy, Sakuma, Sartori, Tenembaum, Van Mater, Wells, Wickstrom, Yeshokumar.

Drafting of the manuscript: Nosadini, Eyre, Molteni, Irani, Dale, M. Lim, Ndondo.

Critical revision of the manuscript for important intellectual content: Nosadini, Eyre, Molteni, Thomas, Dalmau, Dale, M. Lim, Anlar, Armangue, Benseler, Cellucci, Deiva, Gallentine, Gombolay, Gorman, Hacohen, Jiang, B. Lim, Muscal, Ndondo, Neuteboom, Rostásy, Sakuma, Sartori, Sharma, Tenembaum, Van Mater, Wells, Wickstrom, Yeshokumar.

Statistical analysis: Eyre, Molteni, Dale, M. Lim, Benseler.

Obtained funding: Molteni.

Administrative, technical, or material support: Irani, Dale, Cellucci, Gombolay, Jiang.

Study supervision: Dalmau, Dale, M. Lim, Deiva, Sakuma, Sartori, Sharma.

Conflict of Interest Disclosures: Dr Molteni has received grants from the UK Medical Research Council Fellowship Scheme. Dr Irani has received grants from CSL Behring, UCB Pharma, and Ono Pharmaceutical; personal fees from UCB Pharma and ADC Therapeutics; and is a coapplicant and receives royalties on patent application WO/210/046716. Dr Dalmau has received royalties from Euroimmun and grants from SAGE. Dr Ming Lim has received consultation fees from CSL Behring, Novartis, Octapharma, and Roche; grants from Boston Children’s Hospital Research Funds, Great Ormond Street Hospital grant, and Great Ormond Street Hospital/Guy’s and St Thomas’ Trust/St Mary’s Hospital Charity; and has received travel grants from Merck Serono; and was awarded educational grants to organize meetings by Novartis, Biogen Idec, Merck Serono, and Bayer. Dr Armangue has received personal fees from Biogen and Novartis. Dr Cellucci has received personal fees from Novartis Canada. Dr Deiva has received personal fees from Novartis, Biogen, Sanofi, and Viela and nonfinancial support from Novartis. Dr Gombolay receives part-time salary support from the US Centers for Disease Control and Prevention to review acute flaccid myelitis cases for surveillance. Dr Gorman has received research funding from Pfizer and Roche. Dr Neuteboom participates in treatment studies in pediatric multiple sclerosis by Novartis and Sanofi-Genzyme and has received consultation fees from Novartis, Zogenix, and Sanofi-Genzyme. Dr Rostásy participates in treatment studies in pediatric multiple sclerosis by Roche. Dr Tenembaum has received personal fees from Biogen Idec Argentina, Genzyme, Novartis Pharma, Novartis Argentina, Genentech-Roche, and Alexion Pharmaceuticals. Dr Wickstrom has received grants from the Stockholm City Council and Hjärnfonden; consultation fees from Roche, Novartis, and Octapharma; and personal fees from Octapharma, Roche, GW Pharma, and Biogen. Dr Yeshokumar has received personal fees from Bristol Myers Squibb. No other disclosures were reported.

Funding/Support: Dr Eyre is supported by Action Medical Research and the British Paediatric Neurology Association. Dr Molteni is supported by the Medical Research Council Skills Development Fellowship Scheme. Dr Armangue is supported by research grants from Instituto Carlos III/FEDER, Spain (PI18/00486), and Generalitat de Catalunya PERIS (SLT006/17/00362). Dr Irani is supported by the Wellcome Trust (104079/Z/14/Z), the UCB-Oxford University Alliance, BMA Research Grants, Vera Down grant (2013) and Margaret Temple grant (2017), Epilepsy Research UK (P1201), the Fulbright UK-US Commission (Multiple Sclerosis Society research award), and the National Institute for Health Research Oxford Biomedical Research Centre. Dr Dale is supported by National Health and Medical Research Council Investigator grant (Australia) and Petre Foundation. Dr Ming Lim receives research grants from Action Medical Research, the Dancing Eye Syndrome Society, the Great Ormond Street Hospital Charity, the National Institute for Health Research, the Multiple Sclerosis Society UK, and the Sparks Charity; and receives research support grants from the London Clinical Research Network and the Evelina Appeal.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: This study was supported and endorsed by the Autoimmune Encephalitis Alliance. Thank you to Kimberley de Haseth, BSc (Autoimmune Encephalitis Alliance, Durham, North Carolina), for support and advice. She was not compensated for her contribution.

References
1.
Titulaer  MJ , 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(2):157-165. doi:10.1016/S1474-4422(12)70310-1PubMedGoogle ScholarCrossref
2.
de Bruijn  MAAM , Aarsen  FK , van Oosterhout  MP ,  et al; CHANCE Study Group.  Long-term neuropsychological outcome following pediatric anti-NMDAR encephalitis.   Neurology. 2018;90(22):e1997-e2005. doi:10.1212/WNL.0000000000005605PubMedGoogle ScholarCrossref
3.
Irani  SR , Bera  K , Waters  P ,  et al.  N-methyl-d-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes.   Brain. 2010;133(pt 6):1655-1667. doi:10.1093/brain/awq113PubMedGoogle Scholar
4.
Hacohen  Y , Absoud  M , Hemingway  C ,  et al.  NMDA receptor antibodies associated with distinct white matter syndromes.   Neurol Neuroimmunol Neuroinflamm. 2014;1(1):e2. doi:10.1212/NXI.0000000000000002PubMedGoogle Scholar
5.
Byrne  S , Walsh  C , Hacohen  Y ,  et al.  Earlier treatment of NMDAR antibody encephalitis in children results in a better outcome.   Neurol Neuroimmunol Neuroinflamm. 2015;2(4):e130. doi:10.1212/NXI.0000000000000130PubMedGoogle Scholar
6.
Nosadini  M , Granata  T , Matricardi  S ,  et al; Italian Working Group on Paediatric Anti-N-methyl-d-aspartate Receptor Encephalitis.  Relapse risk factors in anti-N-methyl-d-aspartate receptor encephalitis.   Dev Med Child Neurol. 2019;61(9):1101-1107. doi:10.1111/dmcn.14267PubMedGoogle ScholarCrossref
7.
Gabilondo  I , Saiz  A , Galán  L ,  et al.  Analysis of relapses in anti-NMDAR encephalitis.   Neurology. 2011;77(10):996-999. doi:10.1212/WNL.0b013e31822cfc6bPubMedGoogle ScholarCrossref
8.
Dalmau  J , Lancaster  E , Martinez-Hernandez  E , Rosenfeld  MR , Balice-Gordon  R .  Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis.   Lancet Neurol. 2011;10(1):63-74. doi:10.1016/S1474-4422(10)70253-2PubMedGoogle ScholarCrossref
9.
Dale  RC , Gorman  MP , Lim  M .  Autoimmune encephalitis in children: clinical phenomenology, therapeutics, and emerging challenges.   Curr Opin Neurol. 2017;30(3):334-344. doi:10.1097/WCO.0000000000000443PubMedGoogle ScholarCrossref
10.
Lancaster  E .  The diagnosis and treatment of autoimmune encephalitis.   J Clin Neurol. 2016;12(1):1-13. doi:10.3988/jcn.2016.12.1.1PubMedGoogle ScholarCrossref
11.
Shin  YW , Lee  ST , Park  KI ,  et al.  Treatment strategies for autoimmune encephalitis.   Ther Adv Neurol Disord. 2017;11:1756285617722347.PubMedGoogle Scholar
12.
Zuliani  L , Nosadini  M , Gastaldi  M ,  et al.  Management of antibody-mediated autoimmune encephalitis in adults and children: literature review and consensus-based practical recommendations.   Neurol Sci. 2019;40(10):2017-2030. doi:10.1007/s10072-019-03930-3PubMedGoogle ScholarCrossref
13.
Dalmau  J , Armangué  T , Planagumà  J ,  et al.  An update on anti-NMDA receptor encephalitis for neurologists and psychiatrists: mechanisms and models.   Lancet Neurol. 2019;18(11):1045-1057. doi:10.1016/S1474-4422(19)30244-3PubMedGoogle ScholarCrossref
14.
Bartolini  L , Muscal  E .  Differences in treatment of anti-NMDA receptor encephalitis: results of a worldwide survey.   J Neurol. 2017;264(4):647-653. doi:10.1007/s00415-017-8407-1PubMedGoogle ScholarCrossref
15.
Kahn  I , Helman  G , Vanderver  A , Wells  E .  Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis.   J Child Neurol. 2017;32(2):243-245. doi:10.1177/0883073816675557PubMedGoogle ScholarCrossref
16.
Balu  R , McCracken  L , Lancaster  E , Graus  F , Dalmau  J , Titulaer  MJ .  A score that predicts 1-year functional status in patients with anti-NMDA receptor encephalitis.   Neurology. 2019;92(3):e244-e252. doi:10.1212/WNL.0000000000006783PubMedGoogle ScholarCrossref
17.
Graus  F , Titulaer  MJ , Balu  R ,  et al.  A clinical approach to diagnosis of autoimmune encephalitis.   Lancet Neurol. 2016;15(4):391-404. doi:10.1016/S1474-4422(15)00401-9PubMedGoogle ScholarCrossref
18.
van Swieten  JC , Koudstaal  PJ , Visser  MC , Schouten  HJ , van Gijn  J .  Interobserver agreement for the assessment of handicap in stroke patients.   Stroke. 1988;19(5):604-607. doi:10.1161/01.STR.19.5.604PubMedGoogle ScholarCrossref
19.
Sartori  S , Nosadini  M , Cesaroni  E ,  et al.  Paediatric anti-N-methyl-d-aspartate receptor encephalitis: the first Italian multicenter case series.   Eur J Paediatr Neurol. 2015;19(4):453-463. doi:10.1016/j.ejpn.2015.02.006PubMedGoogle ScholarCrossref
20.
Broadley  J , Seneviratne  U , Beech  P ,  et al.  Prognosticating autoimmune encephalitis: a systematic review.   J Autoimmun. 2019;96:24-34. doi:10.1016/j.jaut.2018.10.014PubMedGoogle ScholarCrossref
21.
Cuzick  J .  A Wilcoxon-type test for trend.   Stat Med. 1985;4(1):87-90. doi:10.1002/sim.4780040112PubMedGoogle ScholarCrossref
22.
Andridge  RR , Little  RJ .  A review of hot deck imputation for survey non-response.   Int Stat Rev. 2010;78(1):40-64. doi:10.1111/j.1751-5823.2010.00103.xPubMedGoogle ScholarCrossref
23.
Bar-Shira  O , Maor  R , Chechik  G .  Gene expression switching of receptor subunits in human brain development.   PLoS Comput Biol. 2015;11(12):e1004559. doi:10.1371/journal.pcbi.1004559PubMedGoogle Scholar
24.
Pegasiou  CM , Zolnourian  A , Gomez-Nicola  D ,  et al.  Age-dependent changes in synaptic NMDA receptor composition in adult human cortical neurons.   Cereb Cortex. 2020;30(7):4246-4256. doi:10.1093/cercor/bhaa052PubMedGoogle ScholarCrossref
25.
Shen  CH , Fang  GL , Yang  F ,  et al.  Seizures and risk of epilepsy in anti-NMDAR, anti-LGI1, and anti-GABAB R encephalitis.   Ann Clin Transl Neurol. 2020;7(8):1392-1399. doi:10.1002/acn3.51137PubMedGoogle ScholarCrossref
26.
Sonderen  AV , Arends  S , Tavy  DLJ ,  et al.  Predictive value of electroencephalography in anti-NMDA receptor encephalitis.   J Neurol Neurosurg Psychiatry. 2018;89(10):1101-1106. doi:10.1136/jnnp-2018-318376PubMedGoogle ScholarCrossref
27.
Mo  Y , Wang  L , Zhu  L ,  et al.  Analysis of risk factors for a poor prognosis in patients with anti-N-methyl-d-aspartate receptor encephalitis and construction of a prognostic composite score.   J Clin Neurol. 2020;16(3):438-447. doi:10.3988/jcn.2020.16.3.438PubMedGoogle ScholarCrossref
28.
Bartels  F , Krohn  S , Nikolaus  M ,  et al.  Clinical and magnetic resonance imaging outcome predictors in pediatric anti-N-methyl-d-aspartate receptor encephalitis.   Ann Neurol. 2020;88(1):148-159. doi:10.1002/ana.25754PubMedGoogle ScholarCrossref
29.
Nathoo  N , Anderson  D , Jirsch  J .  Extreme delta brush in anti-NMDAR encephalitis correlates with poor functional outcome and death.   Front Neurol. 2021;12:686521. doi:10.3389/fneur.2021.686521PubMedGoogle Scholar
30.
Schmitt  SE , Pargeon  K , Frechette  ES , Hirsch  LJ , Dalmau  J , Friedman  D .  Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis.   Neurology. 2012;79(11):1094-1100. doi:10.1212/WNL.0b013e3182698cd8PubMedGoogle ScholarCrossref
31.
DeSena  AD , Noland  DK , Matevosyan  K ,  et al.  Intravenous methylprednisolone versus therapeutic plasma exchange for treatment of anti-N-methyl-d-aspartate receptor antibody encephalitis: a retrospective review.   J Clin Apher. 2015;30(4):212-216. doi:10.1002/jca.21363PubMedGoogle ScholarCrossref
32.
Suppiej  A , Nosadini  M , Zuliani  L ,  et al.  Plasma exchange in pediatric anti-NMDAR encephalitis: a systematic review.   Brain Dev. 2016;38(7):613-622. doi:10.1016/j.braindev.2016.01.009PubMedGoogle ScholarCrossref
33.
Sakpichaisakul  K , Patibat  L , Wechapinan  T , Sri-Udomkajrorn  S , Apiwattanakul  M , Suwannachote  S .  Heterogenous treatment for anti-NMDAR encephalitis in children leads to different outcomes 6-12 months after diagnosis.   J Neuroimmunol. 2018;324:119-125. doi:10.1016/j.jneuroim.2018.09.007PubMedGoogle ScholarCrossref
34.
Zhang  L , Wu  MQ , Hao  ZL ,  et al.  Clinical characteristics, treatments, and outcomes of patients with anti-N-methyl-d-aspartate receptor encephalitis: a systematic review of reported cases.   Epilepsy Behav. 2017;68:57-65. doi:10.1016/j.yebeh.2016.12.019PubMedGoogle ScholarCrossref
35.
Zhang  Y , Liu  G , Jiang  M , Chen  W , Su  Y .  Efficacy of therapeutic plasma exchange in patients with severe refractory anti-NMDA receptor encephalitis.   Neurotherapeutics. 2019;16(3):828-837. doi:10.1007/s13311-019-00725-4PubMedGoogle ScholarCrossref
36.
Zheng  J , Shen  J , Wang  A ,  et al.  Clinical characteristics of anti-N-methyl-d-aspartate receptor encephalitis in children.   Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2020;45(1):47-54.PubMedGoogle Scholar
37.
Wright  S , Hacohen  Y , Jacobson  L ,  et al.  N-methyl-d-aspartate receptor antibody-mediated neurological disease: results of a UK-based surveillance study in children.   Arch Dis Child. 2015;100(6):521-526. doi:10.1136/archdischild-2014-306795PubMedGoogle ScholarCrossref
38.
DeSena  AD , Greenberg  BM , Graves  D .  “Light switch” mental status changes and irritable insomnia are two particularly salient features of anti-NMDA receptor antibody encephalitis.   Pediatr Neurol. 2014;51(1):151-153. doi:10.1016/j.pediatrneurol.2013.09.012PubMedGoogle ScholarCrossref
39.
DeSena  AD , Greenberg  BM , 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. doi:10.1016/j.pediatrneurol.2014.04.030PubMedGoogle ScholarCrossref
40.
Thomas  A , Rauschkolb  P , Gresa-Arribas  N , Schned  A , Dalmau  JO , Fadul  CE .  Anti-N-methyl-d-aspartate receptor encephalitis: a patient with refractory illness after 25 months of intensive immunotherapy.   JAMA Neurol. 2013;70(12):1566-1568. doi:10.1001/jamaneurol.2013.3205PubMedGoogle Scholar
41.
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. doi:10.1111/dmcn.12545PubMedGoogle ScholarCrossref
42.
Liba  Z , Kayserova  J , Elisak  M ,  et al.  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. doi:10.1186/s12974-016-0507-9PubMedGoogle ScholarCrossref
43.
Mehr  SR , Neeley  RC , Wiley  M , Kumar  AB .  Profound autonomic instability complicated by multiple episodes of cardiac asystole and refractory bradycardia in a patient with anti-NMDA encephalitis.   Case Rep Neurol Med. 2016;2016:7967526. doi:10.1155/2016/7967526PubMedGoogle Scholar
44.
Jones  HF , Mohammad  SS , Reed  PW ,  et al.  Anti-N-methyl-d-aspartate receptor encephalitis in Māori and Pacific Island children in New Zealand.   Dev Med Child Neurol. 2017;59(7):719-724. doi:10.1111/dmcn.13420PubMedGoogle ScholarCrossref
45.
Behrendt  V , Krogias  C , Reinacher-Schick  A , Gold  R , Kleiter  I .  Bortezomib treatment for patients with anti-N-methyl-d-aspartate receptor encephalitis.   JAMA Neurol. 2016;73(10):1251-1253. doi:10.1001/jamaneurol.2016.2588PubMedGoogle ScholarCrossref
46.
Jun  JS , Seo  HG , Lee  ST , Chu  K , Lee  SK .  Botulinum toxin treatment for hypersalivation in anti-NMDA receptor encephalitis.   Ann Clin Transl Neurol. 2017;4(11):830-834. doi:10.1002/acn3.467PubMedGoogle ScholarCrossref
47.
Janmohamed  M , Knezevic  W , Needham  M , Salman  S .  Primary lateral sclerosis-like picture in a patient with a remote history of anti-N-methyl-d-aspartate receptor (anti-NMDAR) antibody encephalitis.   BMJ Case Rep. 2018;2018:bcr2017224060. doi:10.1136/bcr-2017-224060PubMedGoogle Scholar
48.
Keddie  S , Crisp  SJ , Blackaby  J ,  et al.  Plasma cell depletion with bortezomib in the treatment of refractory N-methyl-d-aspartate (NMDA) receptor antibody encephalitis. rational developments in neuroimmunological treatment.   Eur J Neurol. 2018;25(11):1384-1388. doi:10.1111/ene.13759PubMedGoogle ScholarCrossref
49.
Sveinsson  O , Granqvist  M , Forslin  Y , Blennow  K , Zetterberg  H , Piehl  F .  Successful combined targeting of B- and plasma cells in treatment refractory anti-NMDAR encephalitis.   J Neuroimmunol. 2017;312:15-18. doi:10.1016/j.jneuroim.2017.08.011PubMedGoogle ScholarCrossref
50.
Scheibe  F , Prüss  H , Mengel  AM ,  et al.  Bortezomib for treatment of therapy-refractory anti-NMDA receptor encephalitis.   Neurology. 2017;88(4):366-370. doi:10.1212/WNL.0000000000003536PubMedGoogle ScholarCrossref
51.
Shin  YW , Lee  ST , Kim  TJ , Jun  JS , Chu  K .  Bortezomib treatment for severe refractory anti-NMDA receptor encephalitis.   Ann Clin Transl Neurol. 2018;5(5):598-605. doi:10.1002/acn3.557PubMedGoogle ScholarCrossref
52.
Schroeder  C , Back  C , Koc  Ü ,  et al.  Breakthrough treatment with bortezomib for a patient with anti-NMDAR encephalitis.   Clin Neurol Neurosurg. 2018;172:24-26. doi:10.1016/j.clineuro.2018.06.005PubMedGoogle ScholarCrossref
53.
Yang  XZ , Zhu  HD , Ren  HT ,  et al.  Utility and safety of intrathecal methotrexate treatment in severe anti-N-methyl-d-aspartate receptor encephalitis: a pilot study.   Chin Med J (Engl). 2018;131(2):156-160. doi:10.4103/0366-6999.222327PubMedGoogle ScholarCrossref
54.
Zhang  XT , Wang  CJ , Wang  BJ , Guo  SG .  The short-term efficacy of combined treatments targeting B cell and plasma cell in severe and refractory anti-N-methyl-d-aspartate receptor encephalitis: two case reports.   CNS Neurosci Ther. 2019;25(1):151-153. doi:10.1111/cns.13078PubMedGoogle ScholarCrossref
55.
Lee  W-J , Lee  S-T , Shin  Y-W ,  et al.  Teratoma removal, steroid, IVIG, rituximab and tocilizumab (T-SIRT) in anti-NMDAR encephalitis.   Neurotherapeutics. 2021;18(1):474-487. doi:10.1007/s13311-020-00921-7PubMedGoogle ScholarCrossref
56.
Olsson  T , Barcellos  LF , Alfredsson  L .  Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis.   Nat Rev Neurol. 2017;13(1):25-36. doi:10.1038/nrneurol.2016.187PubMedGoogle ScholarCrossref
57.
Dale  RC , Brilot  F , Duffy  LV ,  et al.  Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease.   Neurology. 2014;83(2):142-150. doi:10.1212/WNL.0000000000000570PubMedGoogle ScholarCrossref
58.
Nosadini  M , Mohammad  SS , Ramanathan  S , Brilot  F , Dale  RC .  Immune therapy in autoimmune encephalitis: a systematic review.   Expert Rev Neurother. 2015;15(12):1391-1419. doi:10.1586/14737175.2015.1115720PubMedGoogle ScholarCrossref
59.
Binks  SNM , Veldsman  M , Easton  A ,  et al.  Residual fatigue and cognitive deficits in patients after leucine-rich glioma-inactivated 1 antibody encephalitis.   JAMA Neurol. 2021;78(5):617-619. doi:10.1001/jamaneurol.2021.0477PubMedGoogle ScholarCrossref
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close