Ovarian teratoma and the anti-N-methyl-D-aspartate receptor encephalitis paraneoplastic phenomenon: A systematic review and analysis of the literature.

Background Paraneoplastic syndromes occurring with germ-cell-tumors (GCTs) are rare but can be life-threatening. Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the commonest GCT-associated paraneoplastic syndrome. We reviewed anti-NMDAR encephalitis associated with ovarian teratomas, aiming to identify key themes regarding presentation and outcomes of treatment. Methods A hybrid, thematic-based PRISMA-compliant review was undertaken. Firstly, a systematic review (English; 1998-2023) describing patients <45y with ovarian teratomas associated with anti-NMDAR encephalitis identified 89 publications, describing 99 patients in sufficient detail. A thematic-based analysis was then undertaken; recovery from encephalitis was defined as: full: patient returning to pre-morbid baseline; partial: ongoing sequalae from disease; none: deterioration, relapse, and/or death. Results Ninety-six of 99 patients (97.0%) had surgery, of which 90 had recovery data. Of these, 12 (13.3%) had surgery alone and 78 (86.7%) adjuvant treatment [chemotherapy (n=21), intravenous immunoglobulin (IVIG)±methylprednisolone (n=74), both (n=17)]. Overall, 56/90 (62.2%) had full, 31/90 (34.4%) partial, and 3/90 (3.3%) no recovery. No differences were observed for full (range 53.0-62.2%) or partial (33.3-47.0%) recovery, with no predictors of full recovery by patient age, rapidity of presentation and/or diagnosis, imaging modality, nor use of adjuvant treatment. There was no difference in outcomes for those patients with oophorectomies compared with ovarian-sparing surgery. Conclusion The addition of adjuvant chemotherapy or immunomodulatory treatments to surgery did not improve outcomes. Where possible, ovarian-sparing surgery should be offered. We recommend judicious use of additional treatments beyond surgery, where evidence remains sparse. A proposed diagnostic algorithm will facilitate prompt identification/treatment of anti-NMDAR encephalitis associated with ovarian teratoma.