Persistent seropositivity in oophorectomy-resistant anti-NMDA receptor encephalitis

To discuss (1) the significance of seropositivity in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and (2) clinical decision making in oophorectomy resistant disease. Patient A (a 35-year-old woman) had high CSF and serum anti-NMDA antibody titres, a complicated hospital course, little improvement with first and second-line therapies, and remained with high CSF and serum antibody titres despite unilateral oophorectomy, requiring a nearly 13-month long hospitalisation. Conversely, patient B (a 29-year-old woman) had low CSF titres, seronegative disease and quickly recovered to her baseline with first line therapies and oophorectomy. Anti-NMDAR antibodies are themselves pathological, causing signalling dysfunction and internalisation of the NMDAR. Seropositivity with anti-NMDAR antibodies likely reflects leakage from the blood-brain barrier, with high serum titres being a downstream effect of high CSF titres. Empiric bilateral oophorectomies is controversial but appropriate on a case-by-case basis in extremely treatment-resistant NMDAR encephalitis given the possibility of antigenic microteratomas, which may not be detected on imaging or even bilateral ovarian biopsies.