著者

飯塚 高浩

出版者

日本神経学会

雑誌

臨床神経学 (ISSN:0009918X)

巻号頁・発行日

vol.49, no.11, pp.774-778, 2009 (Released:2009-12-28)

参考文献数

10

被引用文献数

4 3

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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.