[Unique clinical features and pathophysiology of anti-NMDA receptor encephalitis].
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.
Iizuka
Takahiro
T
Department of Neurology, School of Medicine, Kitasato University.
D001323:Autoantibodies / Q000276:immunology*; D003131:Combined Modality Therapy; D020820:Dyskinesias; D000939:Epitopes; D005260:Female; D006801:Humans; D007167:Immunotherapy; D020363:Limbic Encephalitis / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D010051:Ovarian Neoplasms / Q000601:surgery; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*; D012559:Schizophrenia; D020182:Sleep Apnea, Central; D013724:Teratoma / Q000601:surgery
D001323:Autoantibodies; D000939:Epitopes; D016194:Receptors, N-Methyl-D-Aspartate