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Paraneoplastic anti– N ‐methyl‐ D ‐aspartate receptor encephalitis associated with ovarian teratoma
Open accessAbstract
OBJECTIVE: To report the autoantigens of a new category of treatment-responsive paraneoplastic encephalitis. METHODS: Analysis of clinical features, neuropathological findings, tumors, and serum/cerebrospinal fluid antibodies using rat tissue, neuronal cultures, and HEK293 cells expressing subunits of the N-methyl-D-aspartate receptor (NMDAR). RESULTS: Twelve women (14-44 years) developed prominent psychiatric symptoms, amnesia, seizures, frequent dyskinesias, autonomic dysfunction, and decreased level of consciousness often requiring ventilatory support. All had serum/cerebrospinal fluid antibodies that predominantly immunolabeled the neuropil of hippocampus/forebrain, in particular the cell surface of hippocampal neurons, and reacted with NR2B (and to a lesser extent NR2A) subunits of the NMDAR. NR2B binds glutamate and forms heteromers (NR1/NR2B or NR1/NR2A/NR2B) that are preferentially expressed in the adult hippocampus/forebrain. Expression of functional heteromers (not single subunits) was required for antibody binding. Eleven patients had teratoma of the ovary (six mature) and one a mature teratoma in the mediastinum; five of five tumors examined contained nervous tissue that strongly expressed NR2 subunits and reacted with patients' antibodies. Tumor resection and immunotherapy resulted in improvement or full recovery of eight of nine patients (paralleled by decreased antibody titers); two of three patients without tumor resection died of neurological deterioration. Autopsies showed extensive microgliosis, rare T-cell infiltrates, and neuronal degeneration predominantly involving, but not restricted to, the hippocampus. INTERPRETATION: Antibodies to NR2B- and NR2A-containing heteromers of the NMDAR associate with a severe but treatment-responsive encephalitis. Our findings provide a diagnostic test and suggest a model of autoimmune NMDAR-related encephalitis with broad implications for other immune-mediated disorders of memory, behavior, and cognition.
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“Preliminary studies suggested the target epitopes were located in extracellular regions of NR1–NR2B NMDA receptors.5”
From Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies (2008) · cites this paper as [5]
In the citing paper
“We recently identified a disorder, designated anti-NMDA-receptor encephalitis, that associates with antibodies against NR1–NR2 heteromers and results in a characteristic neuropsychiatric syndrome.5”
From Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies (2008) · cites this paper as [5]
In the citing paper
“The first patients identified were young women with ovarian teratoma who presented with psychosis or memory problems, rapidly progressing to multiple neurological deficits requiring prolonged intensive care support.”
From Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies (2008) · cites this paper as [5]
In the citing paper
“Serum and CSF were tested for antibodies against the NMDA receptor,5 and considered positive if three immunohistochemical criteria were fulfilled (figure 1).”
From Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies (2008) · cites this paper as [5]
In the citing paper
“Despite the severity of the disorder, patients often recovered after tumour removal and immunotherapy, suggesting an immune-mediated pathogenesis.”
From Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies (2008) · cites this paper as [5]
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Citations
Cites
Monyer, H., Burnashev, N., Laurie, D. J., Sakmann, B., & Seeburg, P. H. (1994) · Neuron · doi:10.1016/0896-6273(94)90210-0 · Cited by 3,535
Gultekin, S. H. (2000) · Brain · doi:10.1093/brain/123.7.1481 · Cited by 1,110
Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients
Graus, F. (2001) · Brain · doi:10.1093/brain/124.6.1138 · Cited by 891
DeGiorgio, L. A., Konstantinov, K. N., Lee, S. C., Hardin, J., Volpe, B. T., & Diamond, B. (2001) · Nature Medicine · doi:10.1038/nm1101-1189 · Cited by 798
Clinical analysis of anti-Ma2-associated encephalitis
Dalmau, J. O. (2004) · Brain · doi:10.1093/brain/awh203 · Cited by 776
Antigen unmasking on formalin‐fixed, paraffin‐embedded tissue sections
Cattoretti, G., Pileri, S. A., Parravicini, C., Becker, M. H. G., Poggi, S., Bifulco, C. B., Key, G., D'Amato, L., Sabattini, E., Feudale, E. A. A., et al. (1993) · The Journal of Pathology · doi:10.1002/path.1711710205 · Cited by 721
Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma
Vitaliani, R., Mason, W. P., Ances, B. M., Zwerdling, T., Jiang, Z., & Dalmau, J. O. (2005) · Annals of Neurology · doi:10.1002/ana.20614 · Cited by 604
Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates
Ances, B. M., Vitaliani, R., Taylor, R. A., Liebeskind, D. S., Voloschin, A. D., Houghton, D. J., Galetta, S. L., Dichter, M. A., Alavi, A. A., Rosenfeld, M. R., et al. (2005) · Brain · doi:10.1093/brain/awh526 · Cited by 486
Laube, B., Hirai, H., Sturgess, M., Betz, H., & Kuhse, J. (1997) · Neuron · doi:10.1016/s0896-6273(00)81249-0 · Cited by 476
Wenzel, A., Fritschy, J., Möhler, H., & Benke, D. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.68020469.x · Cited by 442
Kowal, C., DeGiorgio, L. A., Nakaoka, T., Hetherington, H. P., Huerta, P. T., Diamond, B., & Volpe, B. T. (2004) · Immunity · doi:10.1016/j.immuni.2004.07.011 · Cited by 405
Standaert, D. G., Testa, C. M., Young, A. B., & Penney, J. B. (1994) · The Journal of Comparative Neurology · doi:10.1002/cne.903430102 · Cited by 373
N-Methyl-d-aspartate receptor subtypes: multiple roles in excitotoxicity and neurological disease
Waxman, E. A., & Lynch, D. R. (2005) · The Neuroscientist · doi:10.1177/1073858404269012 · Cited by 372
Immunity and behavior: Antibodies alter emotion
Huerta, P. T., Kowal, C., DeGiorgio, L. A., Volpe, B. T., & Diamond, B. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510055103 · Cited by 294
Furneaux, H. M., Rosenblum, M. K., Dalmau, J. O., Wong, E., Woodruff, P., Graus, F., & Posner, J. B. (1990) · New England Journal of Medicine · doi:10.1056/nejm199006283222604 · Cited by 286
Lapteva, L., Nowak, M., Yarboro, C. H., Takada, K., Roebuck‐Spencer, T., Weickert, T. W., Bleiberg, J., Rosenstein, D. L., Pao, M., Patronas, N. J., et al. (2006) · Arthritis & Rheumatism · doi:10.1002/art.22031 · Cited by 259
Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors
Omdal, R., Brokstad, K. A., Waterloo, K. K., Koldingsnes, W., Jonsson, R., & Mellgren, S. I. (2005) · European Journal of Neurology · doi:10.1111/j.1468-1331.2004.00976.x · Cited by 229
Excitotoxicity: Perspectives Based on N-Methyl-d-Aspartate Receptor Subtypes
Lynch, D. R., & Guttmann, R. P. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.300.3.717 · Cited by 196
Lynch, D. R., Anegawa, N. J., Verdoorn, T., & Pritchett, D. B. (1994) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)10028-x · Cited by 173
Voltage‐gated potassium channel antibodies in limbic encephalitis
Pozo‐Rosich, P., Clover, L. M., Saiz, A., Vincent, A. C., & Graus, F. (2003) · Annals of Neurology · doi:10.1002/ana.10713 · Cited by 172
Immunohistochemical analysis of anti-Hu-associated paraneoplastic encephalomyelitis
Bernal, F., Graus, F., Pifarré, À., Saiz, A., Benyahia, B., & Ribalta, T. (2002) · Acta Neuropathologica · doi:10.1007/s00401-001-0498-0 · Cited by 171
Viruses as adjuvants for autoimmunity: evidence from Coxsackievirus‐induced myocarditis
Fairweather, D., Frisancho‐Kiss, S., & Rose, N. R. (2005) · Reviews in Medical Virology · doi:10.1002/rmv.445 · Cited by 155
Viruses, cytokines, antigens, and autoimmunity.
Gianani, R., & Sarvetnick, N. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.6.2257 · Cited by 97
Takahashi, Y., Mori, H., Mishina, M., Watanabe, M., Kondo, N., Shimomura, J., Kubota, Y., Matsuda, K., Fukushima, K., Shiroma, N., et al. (2005) · Epilepsia · doi:10.1111/j.1528-1167.2005.01024.x · Cited by 91
Buchhalter, J., & Dichter, M. A. (1991) · Brain Research Bulletin · doi:10.1016/0361-9230(91)90003-3 · Cited by 90
Transfection of N‐Methyl‐ d ‐Aspartate Receptors in a Nonneuronal Cell Line Leads to Cell Death
Anegawa, N. J., Lynch, D. R., Verdoorn, T. A., & Pritchett, D. B. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.64052004.x · Cited by 83
Lynch, D. R., Lawrence, J. J., Lenz, S. J., Anegawa, N. J., Dichter, M. A., & Pritchett, D. B. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.64041462.x · Cited by 70
Early pathologic findings and long-term improvement in anti-Ma2–associated encephalitis
Blumenthal, D. T., Salzman, K. L., Digre, K. B., Jensen, R. L., Dunson, W. A., & Dalmau, J. O. (2006) · Neurology · doi:10.1212/01.wnl.0000223647.83708.20 · Cited by 62
Kendrick, S. J., Lynch, D. R., & Pritchett, D. B. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.67020608.x · Cited by 53
Koide, R., Shimizu, T., Koike, K., & Dalmau, J. O. (2006) · Journal of Neuro-Oncology · doi:10.1007/s11060-006-9200-7 · Cited by 50
Reversible Paraneoplastic Encephalomyelitis Associated with a Benign Ovarian Teratoma
Taylor, R. B., Mason, W. P., Kong, K., & Wennberg, R. A. (1999) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100000469 · Cited by 47
Grant, E. R., Bacskai, B. J., Pleasure, D., Pritchett, D. B., Gallagher, M. J., Kendrick, S. J., Kricka, L. J., & Lynch, D. R. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.1.647 · Cited by 45
Paraneoplastic limbic encephalitis in a teenage girl with an immature ovarian teratoma
Stein‐Wexler, R., Wootton‐Gorges, S. L., Greco, C. M., & Brunberg, J. A. (2005) · Pediatric Radiology · doi:10.1007/s00247-005-1402-1 · Cited by 42
Immunity and Acquired Alterations in Cognition and Emotion: Lessons from SLE
Diamond, B., Kowal, C., Huerta, P. T., Aranow, C. B., Mackay, M. C., DeGiorgio, L. A., Lee, J., Triantafyllopoulou, A., Cohen-Solal, J. F. G., & Volpe, B. T. (2006) · Advances in immunology · doi:10.1016/s0065-2776(05)89007-8 · Cited by 41
A new cause of limbic encephalopathy
Darnell, R. B., & Posner, J. B. (2005) · Brain · doi:10.1093/brain/awh592 · Cited by 40
Rai, G., Ray, S., Shaw, R. E., DeGrange, P., Mage, R. G., & Newman, B. A. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.1.660 · Cited by 16
A patient with epilepsia partialis continua with anti-glutamate receptor ε2 antibodies
Kumakura, A., Miyajima, T., Fujii, T., Takahashi, Y., & Ito, M. (2003) · Pediatric Neurology · doi:10.1016/s0887-8994(03)00151-6 · Cited by 13
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Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies
Dalmau, J., Gleichman, A. J., Hughes, E. G., Rossi, J. E., Peng, X., Lai, M., Dessain, S. K., Rosenfeld, M. R., Balice-Gordon, R., & Lynch, D. R. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70224-2 · Cited by 3,488
Self-citationTitulaer, M. J., McCracken, L., Gabilondo, I., Armangué, T., Glaser, C., Iizuka, T., Honig, L. S., Benseler, S. M., Kawachi, I., Martinez-Hernandez, E., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70310-1 · Cited by 3,165
Self-citationClinical experience and laboratory investigations in patients with anti-NMDAR encephalitis
Dalmau, J. O., Lancaster, E., Martínez‐Hernández, E., Rosenfeld, M. R., & Balice‐Gordon, R. J. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70253-2 · Cited by 2,428
Lai, M., Huijbers, M. G. M., Lancaster, E., Graus, F., Bataller, L., Balice‐Gordon, R. J., Cowell, J. K., & Dalmau, J. O. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70137-x · Cited by 1,363
Gresa‐Arribas, N., Titulaer, M. J., Torrents, A., Aguilar, E., McCracken, L., Leypoldt, F., Gleichman, A. J., Balice‐Gordon, R. J., Rosenfeld, M. R., Lynch, D. R., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70282-5 · Cited by 1,306
Metadata
- Authors
- Dalmau, J., Tüzün, E., Wu, H., Masjuan, J., Rossi, J. E., Voloschin, A., Baehring, J. M., Shimazaki, H., Koide, R., King, D., Mason, W., Sansing, L. H., Dichter, M. A., Rosenfeld, M. R., & Lynch, D. R.
- Affiliations
- University of Pennsylvania (US)
- Augusta University (US)
- Yale University (US)
- Jichi Medical University (JP)
- Tokyo Metropolitan Neurological Hospital (JP)
- Children's Hospital of Pittsburgh (US)
- Princess Margaret Cancer Centre (CA)
- Corresponding author
- Dalmau, Josep
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2007-01
- Volume
- 61
- Issue
- 1
- Pages
- 25-36
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC2430743
- OpenAlex
- W2114398221
- Cited by
- 2,492
- References
- 37
- Citations by year
- 2026: 105 · 2025: 122 · 2024: 142 · 2023: 135 · 2022: 168 · 2021: 190 · 2020: 158 · 2019: 179 · 2018: 128 · 2017: 152 · 2016: 158 · 2015: 145 · 2014: 129 · 2013: 143 · 2012: 113
- FWCI
- 47.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA089054, R01CA107192)
- National Institute of Neurological Disorders and Stroke (R01NS045986)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Autoimmune Neurological Disorders and Treatments
- Health Sciences › Medicine › Clinical Neurology › Peripheral Neuropathies and Disorders
- Health Sciences › Medicine › Clinical Neurology › Myasthenia Gravis and Thymoma
- Keywords
- paraneoplastic encephalitis, anti-NMDA receptor encephalitis, ovarian teratoma, NMDA receptor subunits, NR2B, NR2A, autoantibodies, hippocampal neurons, autoimmune encephalitis, tumor resection, immunotherapy, microglial activation, neurodegeneration, psychiatric symptoms, amnesia, seizures
- MeSH terms
- Adolescent, Adult, Animals, Antibodies, Dissection, Encephalitis, Female, Humans, Immunohistochemistry, Immunosuppressive Agents, Magnetic Resonance Imaging, Male, Neurons, Ovarian Neoplasms, Teratoma, Transfection, Gene Expression Regulation, Neoplastic, Receptors, N-Methyl-D-Aspartate, Treatment Outcome, Rats, Wistar, Protein Subunits, Rats
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