[Anti-NMDA receptor antibody-mediated encephalitis/encephalopathy].Rinsho Byori. 2009 Mar; 57(3):252-61.RB
Anti-NMDA receptor encephalitis is a treatment-responsive encephalitis associated with anti-NMDA receptor antibodies, which bind to the extracellular conformal epitope in NR1/NR2 heteromers of the NMDA receptor, although recent data have demonstrated that its critical epitope region resides in the NR1 subunit. This disorder usually develops in young women with ovarian teratoma, who typically present with prominent psychiatric symptoms, often preceded by a common cold-like illness. Most cases develop seizures, followed by an unresponsive/catatonic state, prolonged cloudiness of consciousness, central hypoventilation, bizarre dyskinesias, and autonomic symptoms. Brain MRI is often unremarkable. CSF reveals nonspecific changes. EEG usually shows diffuse slowing without paroxysmal discharges. Tumor occurrence was initially believed to be 100%, but now it is estimated to comprise 58% of all cases, 62% in women and 22% in men. The median age at onset is 23 years, but it develops between 5 to 76 years. Although early tumor resection with immunotherapy is recommended, spontaneous recovery also occurs. The pathogenesis remains unknown; however, a recent study demonstrated that the antibodies reversibly inhibit the clustering of the NMDA receptor on the neuronal cell membrane. Based on symptomatology, we speculate that an antibody-mediated inhibition of the NMDA receptor on presynaptic GABAergic interneurons may reduce the release of GABA, causing the disinhibition of postsynaptic glutamatergic transmission, excessive release of glutamate in the prefrontal/subcortical structures, and glutamate and dopamine dysregulation. Acute juvenile female non-herpetic encephalitis (AJFNHE) has been proposed as a distinct clinical entity in Japan independently of tumor presence since 1997, when 5 young women with encephalitis were reported. A recent study suggested that these disorders are identical.