PMID- 17262855
OWN - NLM
STAT- MEDLINE
DCOM- 20070327
LR  - 20220419
IS  - 0364-5134 (Print)
IS  - 1531-8249 (Electronic)
IS  - 0364-5134 (Linking)
VI  - 61
IP  - 1
DP  - 2007 Jan
TI  - Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with 
      ovarian teratoma.
PG  - 25-36
AB  - 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.
FAU - Dalmau, Josep
AU  - Dalmau J
AD  - Department of Neurology, Division of Neuro-oncology, University of Pennsylvania, 
      Philadelphia, PA 19104, USA. josep.dalmau@uphs.upenn.edu
FAU - Tuzun, Erdem
AU  - Tuzun E
FAU - Wu, Hai-yan
AU  - Wu HY
FAU - Masjuan, Jaime
AU  - Masjuan J
FAU - Rossi, Jeffrey E
AU  - Rossi JE
FAU - Voloschin, Alfredo
AU  - Voloschin A
FAU - Baehring, Joachim M
AU  - Baehring JM
FAU - Shimazaki, Haruo
AU  - Shimazaki H
FAU - Koide, Reiji
AU  - Koide R
FAU - King, Dale
AU  - King D
FAU - Mason, Warren
AU  - Mason W
FAU - Sansing, Lauren H
AU  - Sansing LH
FAU - Dichter, Marc A
AU  - Dichter MA
FAU - Rosenfeld, Myrna R
AU  - Rosenfeld MR
FAU - Lynch, David R
AU  - Lynch DR
LA  - eng
GR  - R01 NS045986-04/NS/NINDS NIH HHS/United States
GR  - R01 NS45986/NS/NINDS NIH HHS/United States
GR  - R01CA89054/CA/NCI NIH HHS/United States
GR  - R01 CA107192-04/CA/NCI NIH HHS/United States
GR  - R01 CA107192/CA/NCI NIH HHS/United States
GR  - R01 NS045986/NS/NINDS NIH HHS/United States
GR  - R01CA107192/CA/NCI NIH HHS/United States
GR  - R01 CA089054-05/CA/NCI NIH HHS/United States
GR  - R01 CA089054/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 (Antibodies)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Protein Subunits)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
CIN - Ann Neurol. 2007 Jan;61(1):3-4. PMID: 17262845
CIN - Ann Neurol. 2008 Jul;64(1):110-1; author reply 111-2. PMID: 18350587
CIN - Lancet Psychiatry. 2018 Jan;5(1):9-10. PMID: 29277216
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Antibodies/blood/cerebrospinal fluid/pharmacology
MH  - Dissection/methods
MH  - Encephalitis/*etiology/immunology/metabolism/therapy
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - Immunosuppressive Agents/therapeutic use
MH  - Magnetic Resonance Imaging/methods
MH  - Male
MH  - Neurons/drug effects
MH  - Ovarian Neoplasms/*complications/immunology/metabolism/therapy
MH  - Protein Subunits/immunology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/*immunology/*metabolism
MH  - Teratoma/*complications/immunology/metabolism/therapy
MH  - Transfection/methods
MH  - Treatment Outcome
PMC - PMC2430743
MID - NIHMS45869
EDAT- 2007/01/31 09:00
MHDA- 2007/03/28 09:00
PMCR- 2008/06/18
CRDT- 2007/01/31 09:00
PHST- 2007/01/31 09:00 [pubmed]
PHST- 2007/03/28 09:00 [medline]
PHST- 2007/01/31 09:00 [entrez]
PHST- 2008/06/18 00:00 [pmc-release]
AID - 10.1002/ana.21050 [doi]
PST - ppublish
SO  - Ann Neurol. 2007 Jan;61(1):25-36. doi: 10.1002/ana.21050.