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[Unique clinical features and pathophysiology of anti-NMDA receptor encephalitis].
Rinsho Shinkeigaku. 2009 Nov; 49(11):774-8.RS

Abstract

Recently a new category of treatment-responsive encephalitis has been proposed associated with antibodies against neuronal cell membrane antigens, including VGKC, NMDA receptor (NMDAR) and AMPA receptor. Anti-NMDAR encephalitis is caused by the antibodies, which bind to extracellular conformal epitope in the NR1/NR2 heteromers of the NMDAR. The antibodies are usually detected in CSF/serum of young women with ovarian teratoma (OT), who typically developed schizophrenia-like psychiatric symptoms. Most patients developed seizures, followed by unresponsive/catatonic state, central hypoventilation, and bizarre orofacial-limb dyskinesias. Based on symptomatology and current NMDAR hypofunction hypothesis in schizophrenia, we speculated that the antibodies might cause inhibition of NMDAR in presynaptic GABAergic interneurons, causing a reduction of release of GABA. This results in disinhibition of postsynaptic glutamatergic transmission, excessive release of glutamate in the prefrontal/subcortical structures, and glutamate/dopamine dysregulation. Recent studies demonstrated that the antibodies cause reversible reduction in the numbers of cell-surface NMDAR and NMDAR clusters in postsynaptic dendrites, suggesting antibodies-mediated decreased function of NMDAR. Early tumor resection with immunotherapy is recommended in OT-positive cases but not in OT-negative cases. However, exploratory laparotomy may increase the chance to identify microscopic teratoma and improve the outcome if patients who were refractory to immunotherapy had anti-NMDAR antibodies and ovarian cyst.

Authors+Show Affiliations

Department of Neurology, School of Medicine, Kitasato University.

Pub Type(s)

English Abstract
Journal Article
Review

Language

jpn

PubMed ID

20030207

Citation

Iizuka, Takahiro. "[Unique Clinical Features and Pathophysiology of anti-NMDA Receptor Encephalitis]." Rinsho Shinkeigaku = Clinical Neurology, vol. 49, no. 11, 2009, pp. 774-8.
Iizuka T. [Unique clinical features and pathophysiology of anti-NMDA receptor encephalitis]. Rinsho Shinkeigaku. 2009;49(11):774-8.
Iizuka, T. (2009). [Unique clinical features and pathophysiology of anti-NMDA receptor encephalitis]. Rinsho Shinkeigaku = Clinical Neurology, 49(11), 774-8.
Iizuka T. [Unique Clinical Features and Pathophysiology of anti-NMDA Receptor Encephalitis]. Rinsho Shinkeigaku. 2009;49(11):774-8. PubMed PMID: 20030207.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Unique clinical features and pathophysiology of anti-NMDA receptor encephalitis]. A1 - Iizuka,Takahiro, PY - 2009/12/25/entrez PY - 2009/12/25/pubmed PY - 2010/9/3/medline SP - 774 EP - 8 JF - Rinsho shinkeigaku = Clinical neurology JO - Rinsho Shinkeigaku VL - 49 IS - 11 N2 - Recently a new category of treatment-responsive encephalitis has been proposed associated with antibodies against neuronal cell membrane antigens, including VGKC, NMDA receptor (NMDAR) and AMPA receptor. Anti-NMDAR encephalitis is caused by the antibodies, which bind to extracellular conformal epitope in the NR1/NR2 heteromers of the NMDAR. The antibodies are usually detected in CSF/serum of young women with ovarian teratoma (OT), who typically developed schizophrenia-like psychiatric symptoms. Most patients developed seizures, followed by unresponsive/catatonic state, central hypoventilation, and bizarre orofacial-limb dyskinesias. Based on symptomatology and current NMDAR hypofunction hypothesis in schizophrenia, we speculated that the antibodies might cause inhibition of NMDAR in presynaptic GABAergic interneurons, causing a reduction of release of GABA. This results in disinhibition of postsynaptic glutamatergic transmission, excessive release of glutamate in the prefrontal/subcortical structures, and glutamate/dopamine dysregulation. Recent studies demonstrated that the antibodies cause reversible reduction in the numbers of cell-surface NMDAR and NMDAR clusters in postsynaptic dendrites, suggesting antibodies-mediated decreased function of NMDAR. Early tumor resection with immunotherapy is recommended in OT-positive cases but not in OT-negative cases. However, exploratory laparotomy may increase the chance to identify microscopic teratoma and improve the outcome if patients who were refractory to immunotherapy had anti-NMDAR antibodies and ovarian cyst. SN - 0009-918X UR - https://www.unboundmedicine.com/medline/citation/20030207/[Unique_clinical_features_and_pathophysiology_of_anti_NMDA_receptor_encephalitis]_ L2 - http://joi.jlc.jst.go.jp/JST.JSTAGE/clinicalneurol/49.774?from=PubMed DB - PRIME DP - Unbound Medicine ER -